21 results on '"Adrien S. J. Melquiond"'
Search Results
2. Performance of HADDOCK and a simple contact-based protein-ligand binding affinity predictor in the D3R Grand Challenge 2.
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Zeynep Kurkcuoglu, Panagiotis I. Koukos, Nevia Citro, Mikael E. Trellet, João P. G. L. M. Rodrigues, Irina S. Moreira, Jorge Roel-Touris, Adrien S. J. Melquiond, Cunliang Geng, Jörg Schaarschmidt, Li C. Xue, Anna Vangone, and Alexandre M. J. J. Bonvin
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- 2018
- Full Text
- View/download PDF
3. Robust detection of translocations in lymphoma FFPE samples using targeted locus capture-based sequencing
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Joost Vermaat, Tom van Wezel, Paula J P de Vree, Wouter de Laat, Bauke Ylstra, Amin Allahyar, Marieke Simonis, Harma Feitsma, Adrien S. J. Melquiond, Max van Min, Agata Rakszewska, Erik Splinter, Daphne de Jong, Joost Swennenhuis, Milan Sharma, Mehmet Yilmaz, Arjan Diepstra, Roos J Leguit, Robert van der Geize, Phylicia Stathi, Karima Hajo, Nathalie J. Hijmering, Mark Pieterse, Marjon J.A.M. Verstegen, Peter H.L. Krijger, Ruud W J Meijers, G Tjitske Los-de Vries, Léon C van Kempen, Arjen H.G. Cleven, Pathology, VU University medical center, CCA - Imaging and biomarkers, Hubrecht Institute for Developmental Biology and Stem Cell Research, and Stem Cell Aging Leukemia and Lymphoma (SALL)
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0301 basic medicine ,Tissue Fixation ,Lymphoma ,Non-Hodgkin/diagnosis ,Genes, myc ,General Physics and Astronomy ,Chromosomal translocation ,MYC ,Translocation, Genetic ,0302 clinical medicine ,Cancer genomics ,bcl-2/genetics ,B-Cell/diagnosis ,B-cell lymphoma ,In Situ Hybridization ,In Situ Hybridization, Fluorescence ,Gene Rearrangement ,High-Throughput Nucleotide Sequencing/methods ,Multidisciplinary ,Paraffin Embedding ,medicine.diagnostic_test ,Genes, bcl-2/genetics ,Lymphoma, Non-Hodgkin ,REARRANGEMENTS ,In Situ Hybridization, Fluorescence/methods ,High-Throughput Nucleotide Sequencing ,Proto-Oncogene Proteins c-bcl-6/genetics ,030220 oncology & carcinogenesis ,Proto-Oncogene Proteins c-bcl-6 ,Biomedical engineering ,EXPRESSION ,Lymphoma, B-Cell ,Lymphoma, Non-Hodgkin/diagnosis ,Paraffin Embedding/methods ,Science ,Translocation ,Locus (genetics) ,Computational biology ,Biology ,Fluorescence/methods ,Sensitivity and Specificity ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Genetic ,medicine ,Humans ,Genes, myc/genetics ,Retrospective Studies ,business.industry ,Lymphoma, B-Cell/diagnosis ,Cancer ,B-CELL LYMPHOMA ,Computational Biology ,Reproducibility of Results ,General Chemistry ,Gene rearrangement ,Computational Biology/methods ,medicine.disease ,Personalized medicine ,Genes, bcl-2 ,030104 developmental biology ,Genes ,myc/genetics ,Tissue Fixation/methods ,business ,Fluorescence in situ hybridization - Abstract
In routine diagnostic pathology, cancer biopsies are preserved by formalin-fixed, paraffin-embedding (FFPE) procedures for examination of (intra-) cellular morphology. Such procedures inadvertently induce DNA fragmentation, which compromises sequencing-based analyses of chromosomal rearrangements. Yet, rearrangements drive many types of hematolymphoid malignancies and solid tumors, and their manifestation is instructive for diagnosis, prognosis, and treatment. Here, we present FFPE-targeted locus capture (FFPE-TLC) for targeted sequencing of proximity-ligation products formed in FFPE tissue blocks, and PLIER, a computational framework that allows automated identification and characterization of rearrangements involving selected, clinically relevant, loci. FFPE-TLC, blindly applied to 149 lymphoma and control FFPE samples, identifies the known and previously uncharacterized rearrangement partners. It outperforms fluorescence in situ hybridization (FISH) in sensitivity and specificity, and shows clear advantages over standard capture-NGS methods, finding rearrangements involving repetitive sequences which they typically miss. FFPE-TLC is therefore a powerful clinical diagnostics tool for accurate targeted rearrangement detection in FFPE specimens., Preservation of cancer biopsies by FFPE introduces DNA fragmentation, hindering analysis of rearrangements. Here the authors introduce FFPE Targeted Locus Capture for identification of translocations in preserved samples.
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- 2021
4. Dynamic Control of Selectivity in the Ubiquitination Pathway Revealed by an ASP to GLU Substitution in an Intra-Molecular Salt-Bridge Network.
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Sjoerd J. L. van Wijk, Adrien S. J. Melquiond, Sjoerd Jacob de Vries, H. Th. Marc Timmers, and Alexandre M. J. J. Bonvin
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- 2012
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5. An overview of data‐driven HADDOCK strategies in CAPRI rounds 38‐45
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Adrien S. J. Melquiond, Mikael Trellet, Rodrigo V. Honorato, Jörg Schaarschmidt, Cunliang Geng, Francesco Ambrosetti, Anna Vangone, Zeynep Kurkcuoglu, Jorge Roel-Touris, Li C. Xue, Irina S. Moreira, Panagiotis I. Koukos, and Alexandre M. J. J. Bonvin
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Protein Conformation, alpha-Helical ,Technology ,biomolecular interactions ,Computer science ,computer.software_genre ,Ligands ,Biochemistry ,Force field (chemistry) ,Data-driven ,03 medical and health sciences ,Structural Biology ,Protein Interaction Mapping ,integrative modeling ,Humans ,Desolvation ,Protein Interaction Domains and Motifs ,Amino Acid Sequence ,Linear combination ,Conformational sampling ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,complexes ,Binding Sites ,biology ,030302 biochemistry & molecular biology ,scoring ,Proteins ,Haddock ,prediction ,biology.organism_classification ,Molecular Docking Simulation ,Docking (molecular) ,Research Design ,Structural Homology, Protein ,Thermodynamics ,Model quality ,Protein Conformation, beta-Strand ,Data mining ,Protein Multimerization ,Peptides ,ddc:600 ,computer ,Software ,Protein Binding - Abstract
Our information-driven docking approach HADDOCK has demonstrated a sustained performance since the start of its participation to CAPRI. This is due, in part, to its ability to integrate data into the modeling process, and to the robustness of its scoring function. We participated in CAPRI both as server and manual predictors. In CAPRI rounds 38-45, we have used various strategies depending on the available information. These ranged from imposing restraints to a few residues identified from literature as being important for the interaction, to binding pockets identified from homologous complexes or template-based refinement/CA-CA restraint-guided docking from identified templates. When relevant, symmetry restraints were used to limit the conformational sampling. We also tested for a large decamer target a new implementation of the MARTINI coarse-grained force field in HADDOCK. Overall, we obtained acceptable or better predictions for 13 and 11 server and manual submissions, respectively, out of the 22 interfaces. Our server performance (acceptable or higher-quality models when considering the top 10) was better (59%) than the manual (50%) one, in which we typically experiment with various combinations of protocols and data sources. Again, our simple scoring function based on a linear combination of intermolecular van der Waals and electrostatic energies and an empirical desolvation term demonstrated a good performance in the scoring experiment with a 63% success rate across all 22 interfaces. An analysis of model quality indicates that, while we are consistently performing well in generating acceptable models, there is room for improvement for generating/identifying higher quality models.
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- 2020
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6. An overview of data-driven HADDOCK strategies in CAPRI rounds 38-45
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Panagiotis I. Koukos, Rodrigo V. Honorato, Jorge Roel-Touris, Irina S. Moreira, Adrien S. J. Melquiond, Mikael Trellet, Cunliang Geng, Zeynep Kurkcuoglu, Alexandre M. J. J. Bonvin, Francesco Ambrosetti, Anna Vangone, Li C. Xue, and Jörg Schaarschmidt
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0303 health sciences ,biology ,Computer science ,Haddock ,010402 general chemistry ,biology.organism_classification ,computer.software_genre ,01 natural sciences ,Force field (chemistry) ,0104 chemical sciences ,Data-driven ,03 medical and health sciences ,Desolvation ,Data mining ,Conformational sampling ,computer ,030304 developmental biology - Abstract
Our information-driven docking approach HADDOCK has demonstrated a sustained performance since the start of its participation to CAPRI. This is due, in part, to its ability to integrate data into the modelling process, and to the robustness of its scoring function. We participated in CAPRI both as server and as manual predictors.In CAPRI rounds 38-45, we have used various strategies depending on the information at hand. These ranged from imposing restraints to a few residues identified from literature as being important for the interaction, to binding pockets identified from homologous complexes or template-based refinement / CA-CA restraint-guided docking from identified templates. When relevant, symmetry restraints were used to limit the conformational sampling. We also tested for a large decamer target a new implementation of the MARTINI coarse-grained force field in HADDOCK. Overall in the current rounds, we obtained acceptable or better predictions for 13 and 11 server and manual submissions, respectively, out of the 22 interfaces. Our server performance (acceptable models) was better (59%) than the manual (50%) one, in which we typically experiment with various combinations of protocols and data sources. Again, our simple scoring function based on a linear combination of intermolecular van der Waals and electrostatic energies and an empirical desolvation term demonstrated a good performance in the scoring experiment with a 63% success rate across all 22 interfaces.An analysis of model quality indicates that, while we are consistently performing well in generating acceptable models, there is room for improvement for generating/identifying higher quality models.
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- 2019
- Full Text
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7. Molecular dynamics characterization of the conformational landscape of small peptides: A series of hands-on collaborative practical sessions for undergraduate students
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Adrien S. J. Melquiond, Alexandre M. J. J. Bonvin, and João P. G. L. M. Rodrigues
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0301 basic medicine ,Structure (mathematical logic) ,Class (computer programming) ,4. Education ,Teaching method ,05 social sciences ,GRASP ,050301 education ,Bioinformatics ,Virtualization ,computer.software_genre ,Biochemistry ,Data science ,Popularity ,Characterization (materials science) ,03 medical and health sciences ,030104 developmental biology ,Web page ,0503 education ,Molecular Biology ,computer - Abstract
Molecular modelling and simulations are nowadays an integral part of research in areas ranging from physics to chemistry to structural biology, as well as pharmaceutical drug design. This popularity is due to the development of high-performance hardware and of accurate and efficient molecular mechanics algorithms by the scientific community. These improvements are also benefitting scientific education. Molecular simulations, their underlying theory, and their applications are particularly difficult to grasp for undergraduate students. Having hands-on experience with the methods contributes to a better understanding and solidification of the concepts taught during the lectures. To this end, we have created a computer practical class, which has been running for the past five years, composed of several sessions where students characterize the conformational landscape of small peptides using molecular dynamics simulations in order to gain insights on their binding to protein receptors. In this report, we detail the ingredients and recipe necessary to establish and carry out this practical, as well as some of the questions posed to the students and their expected results. Further, we cite some examples of the students' written reports, provide statistics, and share their feedbacks on the structure and execution of the sessions. These sessions were implemented alongside a theoretical molecular modelling course but have also been used successfully as a standalone tutorial during specialized workshops. The availability of the material on our web page also facilitates this integration and dissemination and lends strength to the thesis of open-source science and education.
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- 2016
8. Blind prediction of interfacial water positions in CAPRI
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Pravin Muthu, Joy Sarmiento, John Wieting, Thom Vreven, Hasup Lee, Dima Kozakov, Haruki Nakamura, Julie C. Mitchell, Juan Fernández-Recio, Haim J. Wolfson, Sergei Grudinin, Yuko Tsuchiya, Iain H. Moal, Efrat Farkash, Chiara Pallara, Petras J. Kundrotas, Howook Hwang, Chaok Seok, Panagiotis L. Kastritis, Hahnbeom Park, Xiaoqin Zou, Junsu Ko, Justyna Aleksandra Wojdyla, Brian G. Pierce, Christophe Schmitz, Colin Kleanthous, Sanbo Qin, Shoshana J. Wodak, Paul A. Bates, Matsuyuki Shirota, Solène Grosdidier, Idit Buch, Ilya A. Vakser, Krishna Praneeth Kilambi, Jianqing Xu, Matthieu Chavent, Sandor Vajda, Adrien S. J. Melquiond, Marc F. Lensink, Shen You Huang, Martin Zacharias, David W. Ritchie, Brian Jiménez-García, Marc van Dijk, Ezgi Karaca, Yoichi Murakami, Daron M. Standley, Albert Solernou, Laura Pérez-Cano, Yang Shen, Miriam Eisenstein, Jeffrey J. Gray, Alexandre M. J. J. Bonvin, Zhiping Weng, Georgy Derevyanko, Kengo Kinoshita, Huan-Xiang Zhou, and Eiji Kanamori
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0303 health sciences ,010304 chemical physics ,Chemistry ,01 natural sciences ,Biochemistry ,Molecular Docking Simulation ,Force field (chemistry) ,Protein–protein interaction ,03 medical and health sciences ,Crystallography ,Molecular recognition ,Protein structure ,Structural Biology ,Docking (molecular) ,0103 physical sciences ,Critical assessment ,Macromolecular docking ,Biological system ,Molecular Biology ,030304 developmental biology - Abstract
We report the first assessment of blind predictions of water positions at protein-protein interfaces, performed as part of the critical assessment of predicted interactions (CAPRI) community-wide experiment. Groups submitting docking predictions for the complex of the DNase domain of colicin E2 and Im2 immunity protein (CAPRI Target 47), were invited to predict the positions of interfacial water molecules using the method of their choice. The predictions-20 groups submitted a total of 195 models-were assessed by measuring the recall fraction of water-mediated protein contacts. Of the 176 high- or medium-quality docking models-a very good docking performance per se-only 44% had a recall fraction above 0.3, and a mere 6% above 0.5. The actual water positions were in general predicted to an accuracy level no better than 1.5 A, and even in good models about half of the contacts represented false positives. This notwithstanding, three hotspot interface water positions were quite well predicted, and so was one of the water positions that is believed to stabilize the loop that confers specificity in these complexes. Overall the best interface water predictions was achieved by groups that also produced high-quality docking models, indicating that accurate modelling of the protein portion is a determinant factor. The use of established molecular mechanics force fields, coupled to sampling and optimization procedures also seemed to confer an advantage. Insights gained from this analysis should help improve the prediction of protein-water interactions and their role in stabilizing protein complexes.
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- 2013
9. Prediction of homo- and hetero-protein complexes by protein docking and template-based modeling: a CASP-CAPRI experiment
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Eichiro Ichiishi, Dmitri Beglov, Bernard Maigret, Gyu Rie Lee, Artem B. Mamonov, Shoshana J. Wodak, Jonathan C. Fuller, Dima Kozakov, Jong Young Joung, Petr Popov, Xiaofeng Yu, Keehyoung Joo, João P. G. L. M. Rodrigues, Anna Vangone, Koen M. Visscher, Xiaoqin Zou, Paul A. Bates, Andriy Kryshtafovych, Shourya S. Roy Burman, Daisuke Kihara, Romina Oliva, Efrat Ben-Zeev, Jeffrey J. Gray, Yang Shen, Li C. Xue, Sameer Velankar, Emilie Neveu, Shruthi Viswanath, Dina Schneidman-Duhovny, Juan Esquivel-Rodríguez, Mieczyslaw Torchala, Amit Roy, Alexandre M. J. J. Bonvin, David R. Hall, Tanggis Bohnuud, Xusi Han, David W. Ritchie, Ron Elber, Daisuke Kuroda, Zhiwei Ma, Joan Segura, Carlos A. Del Carpio, Nicholas A. Marze, Jong Yun Kim, Andrej Sali, Petras J. Kundrotas, Ezgi Karaca, Neil J. Bruce, Chaok Seok, Panagiotis L. Kastritis, Shen You Huang, Ilya A. Vakser, Lim Heo, Sanbo Qin, Raphael A. G. Chaleil, Adrien S. J. Melquiond, Miguel Romero-Durana, Anisah W. Ghoorah, Surendra S. Negi, Andrey Tovchigrechko, Françoise Ochsenbein, Narcis Fernandez-Fuentes, Liming Qiu, Miriam Eisenstein, Mehdi Nellen, Marie-Dominique Devignes, Lenna X. Peterson, Jinchao Yu, Minkyung Baek, Brian G. Pierce, Hasup Lee, Toshiyuki Oda, Rebecca C. Wade, Raphael Guerois, Juan Fernández-Recio, Iain H. Moal, Edrisse Chermak, Sergei Grudinin, Sangwoo Park, Ivan Anishchenko, Chengfei Yan, Thom Vreven, Kentaro Tomii, Bing Xia, Hyung Rae Kim, Chiara Pallara, Jooyoung Lee, Kazunori D. Yamada, Xianjin Xu, Kenichiro Imai, Zhiping Weng, Luigi Cavallo, Tyler M. Borrman, Jianlin Cheng, Marc F. Lensink, Huan-Xiang Zhou, Jilong Li, Gydo C. P. van Zundert, Brian Jiménez-García, Tsukasa Nakamura, Scott E. Mottarella, Sandor Vajda, Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] ( IRI ), Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), European Molecular Biology Laboratory, European Bioinformatics Institute, Genome Center [UC Davis], University of California at Davis, Research Support Computing [Columbia], University of Missouri-Columbia, Bioinformatics Consortium and Department of Computer Science [Columbia], Department of Bioengineering and Therapeutic Sciences, University of California [San Francisco] ( UCSF ), Department of Pharmaceutical Chemistry, Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, University of California [San Francisco] ( UCSF ) -California Institute for Quantitative Biosciences, GN7 of the National Institute for Bioinformatics (INB) and Biocomputing Unit, Centro Nacional de Biotecnología (CSIC), Institute of Biological, Environmental and Rural Sciences ( IBERS ), Institute for Computational Engineering and Sciences [Austin] ( ICES ), University of Texas at Austin [Austin], Department of Computer Science, Department of Chemistry, Algorithms for Modeling and Simulation of Nanosystems ( NANO-D ), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Laboratoire Jean Kuntzmann ( LJK ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Institut National Polytechnique de Grenoble ( INPG ), Moscow Institute of Physics and Technology [Moscow] ( MIPT ), Seoul National University [Seoul], Florida State University [Tallahassee] ( FSU ), Computational Algorithms for Protein Structures and Interactions ( CAPSID ), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Department of Complex Systems, Artificial Intelligence & Robotics ( LORIA - AIS ), Laboratoire Lorrain de Recherche en Informatique et ses Applications ( LORIA ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ) -Laboratoire Lorrain de Recherche en Informatique et ses Applications ( LORIA ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), University of Mauritius, Biomolecular Modelling Laboratory, The Francis Crick Institute, Lincoln's Inn Fields Laboratory, G-INCPM, Weizmann Institute of Science, Chemical Research Support [Rehovot], Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch ( UTMB ), Program in Bioinformatics and Integrative Biology [Worcester], University of Massachusetts Medical School [Worcester] ( UMASS ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Bijvoet Center for Biomolecular Research [Utrecht], Utrecht University [Utrecht], Dalton Cardiovascular Research Center [Columbia], Department of Computer Science [Columbia], Informatics Intitute, Department of Biochemistry, University of Missouri, UNIVERSITY OF MISSOURI, Toyota Technological Institute at Chicago [Chicago] ( TTIC ), Department of Biological Sciences, Purdue University, Purdue University [West Lafayette], Department of Computer Science [Purdue], Bioinformatics and Computational Biosciences Branch, Rocky Mountain Laboratories, Molecular and Cellular Modeling Group, Heidelberg Institute of Theoretical Studies, Center for Molecular Biology ( ZMBH ), Universität Heidelberg [Heidelberg], Interdisciplinary Center for Scientific Computing ( IWR ), Department of Molecular Biosciences [Lawrence], University of Kansas [Lawrence] ( KU ), Computational Biology Research Center ( CBRC ), National Institute of Advanced Industrial Science and Technology ( AIST ), Graduate School of Frontier Sciences, The University of Tokyo, Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona Supercomputing Center - Centro Nacional de Supercomputacion ( BSC - CNS ), Center for In-Silico Protein Science, Korea Institute for Advanced Study ( KIAS ), Center for Advanced Computation, Department of Biomedical Engineering [Boston], Boston University [Boston] ( BU ), Institute of Biological Diversity, International Pacific Institute of Indiana, Drosophila Genetic Resource Center, Kyoto Institute of Technology, International University of Health and Welfare Hospital ( IUHW Hospital ), International University of Health and Welfare Hospital, Department of Chemical and Biomolecular Engineering [Baltimore], Johns Hopkins University ( JHU ), Program in Molecular Biophysics [Baltimore], King Abdullah University of Science and Technology ( KAUST ), University of Naples, J Craig Venter Institute, Structural Biology Research Center, VIB, 1050 Brussels, Belgium, Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] (IRI), Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, University of California [Davis] (UC Davis), University of California (UC)-University of California (UC), University of Missouri [Columbia] (Mizzou), University of Missouri System, University of California [San Francisco] (UC San Francisco), Centro Nacional de Biotecnología [Madrid] (CNB-CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Institute of Biological, Environmental and Rural Sciences (IBERS), Institute for Computational Engineering and Sciences [Austin] (ICES), Algorithms for Modeling and Simulation of Nanosystems (NANO-D), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Laboratoire Jean Kuntzmann (LJK ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Moscow Institute of Physics and Technology [Moscow] (MIPT), Seoul National University [Seoul] (SNU), Florida State University [Tallahassee] (FSU), Computational Algorithms for Protein Structures and Interactions (CAPSID), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Biomolecular Modelling Laboratory [London], The Francis Crick Institute [London], Weizmann Institute of Science [Rehovot, Israël], The University of Texas Medical Branch (UTMB), University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS)-University of Massachusetts System (UMASS), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Assemblage moléculaire et intégrité du génome (AMIG), Département Biochimie, Biophysique et Biologie Structurale (B3S), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), University of Missouri System-University of Missouri System, Toyota Technological Institute at Chicago [Chicago] (TTIC), Department of Biological Sciences [Lafayette IN], Heidelberg Institute for Theoretical Studies (HITS ), Center for Molecular Biology (ZMBH), Universität Heidelberg [Heidelberg] = Heidelberg University, Interdisciplinary Center for Scientific Computing (IWR), University of Kansas [Lawrence] (KU), Computational Biology Research Center (CBRC), National Institute of Advanced Industrial Science and Technology (AIST), The University of Tokyo (UTokyo), Barcelona Supercomputing Center - Centro Nacional de Supercomputacion (BSC - CNS), Korea Institute for Advanced Study (KIAS), Boston University [Boston] (BU), International University of Health and Welfare Hospital (IUHW Hospital), Johns Hopkins University (JHU), King Abdullah University of Science and Technology (KAUST), University of Naples Federico II = Università degli studi di Napoli Federico II, J. Craig Venter Institute, VIB-VUB Center for Structural Biology [Bruxelles], VIB [Belgium], Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé-Université de Lille, Sciences et Technologies, University of California-University of California, University of California [San Francisco] (UCSF), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), University of Naples Federico II, Barcelona Supercomputing Center, NMR Spectroscopy, and Sub NMR Spectroscopy
- Subjects
0301 basic medicine ,Protein Conformation, alpha-Helical ,Protein Folding ,Computer science ,International Cooperation ,Amino Acid Motifs ,Oligomer state ,Homoprotein ,DATA-BANK ,computer.software_genre ,Molecular Docking Simulation ,Biochemistry ,CAPRI Round 30 ,DESIGN ,Structural Biology ,ALIGN ,Blind prediction ,AFFINITY ,Protein interaction ,Enginyeria biomèdica [Àrees temàtiques de la UPC] ,ZDOCK ,Oligomer State ,computer.file_format ,Articles ,Protein structure prediction ,Proteïnes--Investigació ,3. Good health ,WEB SERVER ,CASP ,Thermodynamics ,Data mining ,CAPRI ,Protein docking ,Molecular Biology ,Algorithms ,INTERFACES ,Protein Binding ,[ INFO.INFO-MO ] Computer Science [cs]/Modeling and Simulation ,Bioinformatics ,STRUCTURAL BIOLOGY ,Computational biology ,Molecular Dynamics Simulation ,Article ,03 medical and health sciences ,[ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM] ,Heteroprotein ,Humans ,Protein binding ,Macromolecular docking ,Protein Interaction Domains and Motifs ,Homology modeling ,ALGORITHM ,Protein-protein docking ,Internet ,Binding Sites ,Models, Statistical ,030102 biochemistry & molecular biology ,Bacteria ,Sequence Homology, Amino Acid ,Computational Biology ,Proteins ,Protein Data Bank ,[INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation ,Protein Structure, Tertiary ,030104 developmental biology ,Structural biology ,Docking (molecular) ,Protein structure ,Protein Conformation, beta-Strand ,Protein Multimerization ,oligomer state ,blind prediction ,protein interaction ,protein docking ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] ,computer ,Software - Abstract
We present the results for CAPRI Round 30, the first joint CASP-CAPRI experiment, which brought together experts from the protein structure prediction and protein–protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. The targets included mostly homodimers, a few homotetramers, and two heterodimers, and comprised protein chains that could readily be modeled using templates from the Protein Data Bank. On average 24 CAPRI groups and 7 CASP groups submitted docking predictions for each target, and 12 CAPRI groups per target participated in the CAPRI scoring experiment. In total more than 9500 models were assessed against the 3D structures of the corresponding target complexes. Results show that the prediction of homodimer assemblies by homology modeling techniques and docking calculations is quite successful for targets featuring large enough subunit interfaces to represent stable associations. Targets with ambiguous or inaccurate oligomeric state assignments, often featuring crystal contact-sized interfaces, represented a confounding factor. For those, a much poorer prediction performance was achieved, while nonetheless often providing helpful clues on the correct oligomeric state of the protein. The prediction performance was very poor for genuine tetrameric targets, where the inaccuracy of the homology-built subunit models and the smaller pair-wise interfaces severely limited the ability to derive the correct assembly mode. Our analysis also shows that docking procedures tend to perform better than standard homology modeling techniques and that highly accurate models of the protein components are not always required to identify their association modes with acceptable accuracy. We are most grateful to the PDBe at the European Bioinformatics Institute in Hinxton, UK, for hosting the CAPRI website. Our deepest thanks go to all the structural biologists and to the following structural genomics initiatives: Northeast Structural Genomics Consortium, Joint Center for Structural Genomics, NatPro PSI:Biology, New York Structural Genomics Research Center, Midwest Center for Structural Genomics, Structural Genomics Consortium, for contributing the targets for this joint CASP-CAPRI experiment. MFL acknowledges support from the FRABio FR3688 Research Federation “Structural & Functional Biochemistry of Biomolecular Assemblies.”
- Published
- 2016
10. Enhancers reside in a unique epigenetic environment during early zebrafish development
- Author
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Geert Geeven, Andrew D. Smith, Christof Niehrs, Wouter de Laat, Michael U. Musheev, Ren� F. Ketting, Ant�nio M. de Jesus Domingues, Michal Mokry, Adrien S. J. Melquiond, Meng Zhou, Lucas J.T. Kaaij, and Hubrecht Institute for Developmental Biology and Stem Cell Research
- Subjects
0301 basic medicine ,Evolution ,Embryonic Development ,Epigenesis, Genetic ,03 medical and health sciences ,chemistry.chemical_compound ,Behavior and Systematics ,Gene expression ,Genetics ,Journal Article ,Enhancers ,Animals ,Epigenetics ,Enhancer ,Zebrafish ,4C ,Ecology, Evolution, Behavior and Systematics ,DNA methylation ,Ecology ,biology ,Research ,Gene Expression Regulation, Developmental ,Promoter ,Cell Differentiation ,Cell Biology ,Zebrafish development ,biology.organism_classification ,Human genetics ,030104 developmental biology ,Enhancer Elements, Genetic ,chemistry ,Priming ,Transcription Initiation Site ,DNA - Abstract
Background Enhancers, not promoters, are the most dynamic in their DNA methylation status throughout development and differentiation. Generally speaking, enhancers that are primed to or actually drive gene expression are characterized by relatively low levels of DNA methylation (hypo-methylation), while inactive enhancers display hyper-methylation of the underlying DNA. The direct functional significance of the DNA methylation state of enhancers is, however, unclear for most loci. Results In contrast to conventional epigenetic interactions at enhancers, we find that DNA methylation status and enhancer activity during early zebrafish development display very unusual correlation characteristics: hypo-methylation is a unique feature of primed enhancers whereas active enhancers are generally hyper-methylated. The hypo-methylated enhancers that we identify (hypo-enhancers) are enriched close to important transcription factors that act later in development. Interestingly, hypo-enhancers are de-methylated shortly before the midblastula transition and reside in a unique epigenetic environment. Finally, we demonstrate that hypo-enhancers do become active at later developmental stages and that they are physically associated with the transcriptional start site of target genes, irrespective of target gene activity. Conclusions We demonstrate that early development in zebrafish embodies a time window characterized by non-canonical DNA methylation–enhancer relationships, including global DNA hypo-methylation of inactive enhancers and DNA hyper-methylation of active enhancers. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1013-1) contains supplementary material, which is available to authorized users.
- Published
- 2016
11. Next challenges in protein-protein docking: from proteome to interactome and beyond
- Author
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Adrien S. J. Melquiond, Ezgi Karaca, Panagiotis L. Kastritis, and Alexandre M. J. J. Bonvin
- Subjects
0303 health sciences ,Protein protein ,030302 biochemistry & molecular biology ,Structural dimension ,Nanotechnology ,Computational biology ,Biology ,Biochemistry ,Interactome ,Computer Science Applications ,03 medical and health sciences ,Computational Mathematics ,Structural biology ,Modelling methods ,Docking (molecular) ,Proteome ,Materials Chemistry ,Macromolecular docking ,Physical and Theoretical Chemistry ,030304 developmental biology - Abstract
Advances in biophysics and biochemistry have pushed back the limits for the structural characterization of biomolecular assemblies. Large efforts have been devoted to increase both resolution and accuracy of the methods, probe into the smallest biomolecules as well as the largest macromolecular machineries, unveil transient complexes along with dynamic interaction processes, and, lately, dissect whole organism interactomes using high-throughput strategies. However, the atomic description of such interactions, rarely reached by large-scale projects in structural biology, remains indispensable to fully understand the subtleties of therecognitionprocess,measuretheimpactofamutationorpredicttheeffectofa drug binding to a complex. Mixing even a limited amount of experimental and/or bioinformatic data with modeling methods, such as macromolecular docking, presents a valuable strategy to predict the three-dimensional structures of complexes. Recent developments indicate that the docking community is seething to tackle the greatest challenge of adding the structural dimension to interactomes. C � 2011 John Wiley & Sons, Ltd.
- Published
- 2011
12. Building Macromolecular Assemblies by Information-driven Docking
- Author
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Ezgi Karaca, Sjoerd J. de Vries, Panagiotis L. Kastritis, Alexandre M. J. J. Bonvin, and Adrien S. J. Melquiond
- Subjects
0303 health sciences ,biology ,Computer science ,030302 biochemistry & molecular biology ,Structural dimension ,Haddock ,biology.organism_classification ,Biochemistry ,Analytical Chemistry ,Computational science ,03 medical and health sciences ,Critical Assessment of Prediction of Interactions ,Docking (molecular) ,DOCK ,Experimental methods ,User interface ,Molecular Biology ,Simulation ,030304 developmental biology ,Macromolecule - Abstract
Over the last years, large scale proteomics studies have generated a wealth of information of biomolecular complexes. Adding the structural dimension to the resulting interactomes represents a major challenge that classical structural experimental methods alone will have difficulties to confront. To meet this challenge, complementary modeling techniques such as docking are thus needed. Among the current docking methods, HADDOCK (High Ambiguity-Driven DOCKing) distinguishes itself from others by the use of experimental and/or bioinformatics data to drive the modeling process and has shown a strong performance in the critical assessment of prediction of interactions (CAPRI), a blind experiment for the prediction of interactions. Although most docking programs are limited to binary complexes, HADDOCK can deal with multiple molecules (up to six), a capability that will be required to build large macromolecular assemblies. We present here a novel web interface of HADDOCK that allows the user to dock up to six biomolecules simultaneously. This interface allows the inclusion of a large variety of both experimental and/or bioinformatics data and supports several types of cyclic and dihedral symmetries in the docking of multibody assemblies. The server was tested on a benchmark of six cases, containing five symmetric homo-oligomeric protein complexes and one symmetric protein-DNA complex. Our results reveal that, in the presence of either bioinformatics and/or experimental data, HADDOCK shows an excellent performance: in all cases, HADDOCK was able to generate good to high quality solutions and ranked them at the top, demonstrating its ability to model symmetric multicomponent assemblies. Docking methods can thus play an important role in adding the structural dimension to interactomes. However, although the current docking methodologies were successful for a vast range of cases, considering the variety and complexity of macromolecular assemblies, inclusion of some kind of experimental information (e. g. from mass spectrometry, nuclear magnetic resonance, cryoelectron microscopy, etc.) will remain highly desirable to obtain reliable results. Molecular & Cellular Proteomics 9:1784-1794, 2010.
- Published
- 2010
13. Data-driven Docking: Using External Information to Spark the Biomolecular Rendez-vous
- Author
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Adrien S. J. Melquiond and Alexandre M. J. J. Bonvin
- Subjects
0303 health sciences ,03 medical and health sciences ,010304 chemical physics ,Docking (molecular) ,Computer science ,0103 physical sciences ,01 natural sciences ,Simulation ,030304 developmental biology ,Data-driven - Published
- 2010
- Full Text
- View/download PDF
14. Role of the Region 23-28 in Aβ Fibril Formation: Insights from Simulations of the Monomers and Dimers of Alzheimers Peptides Aβ40 and Aβ42
- Author
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Philippe Derreumaux, Xiao Dong, Adrien S. J. Melquiond, and Normand Mousseau
- Subjects
chemistry.chemical_classification ,Chemistry ,Stereochemistry ,Peptide ,Limiting ,medicine.disease ,Amino acid ,chemistry.chemical_compound ,Fibril formation ,Monomer ,Neurology ,Biochemistry ,medicine ,Neurology (clinical) ,Alzheimer's disease - Abstract
Self-assembly of the 40/42 amino acid A! peptide is a key player in Alzheimer's disease. A! 40 is the most prevalent species, while A! 42 is the most toxic. It has been suggested that the amino acids 21-30 could nucleate the fold- ing of A! monomer and a bent in this region could be the rate-limiting step in A! fibril formation. In this study, we review our current understanding of the computer-predicted conformations of amino acids 23-28 in the monomer of A! (21-30) and the monomers A! 40 and A! 42. On the basis of new simulations on dimers of full-length A! , we propose that the rate- limiting step involves the formation of a multimeric ! -sheet spanning the central hydrophobic core (residues 17-21).
- Published
- 2008
15. Information-driven modeling of protein-peptide complexes
- Author
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Mikael, Trellet, Adrien S J, Melquiond, and Alexandre M J J, Bonvin
- Subjects
Models, Molecular ,Molecular Docking Simulation ,Protein Interaction Mapping ,Molecular Conformation ,Proteins ,Peptides ,Algorithms ,Software ,Protein Binding - Abstract
Despite their biological importance in many regulatory processes, protein-peptide recognition mechanisms are difficult to study experimentally at the structural level because of the inherent flexibility of peptides and the often transient interactions on which they rely. Complementary methods like biomolecular docking are therefore required. The prediction of the three-dimensional structure of protein-peptide complexes raises unique challenges for computational algorithms, as exemplified by the recent introduction of protein-peptide targets in the blind international experiment CAPRI (Critical Assessment of PRedicted Interactions). Conventional protein-protein docking approaches are often struggling with the high flexibility of peptides whose short sizes impede protocols and scoring functions developed for larger interfaces. On the other side, protein-small ligand docking methods are unable to cope with the larger number of degrees of freedom in peptides compared to small molecules and the typically reduced available information to define the binding site. In this chapter, we describe a protocol to model protein-peptide complexes using the HADDOCK web server, working through a test case to illustrate every steps. The flexibility challenge that peptides represent is dealt with by combining elements of conformational selection and induced fit molecular recognition theories.
- Published
- 2015
16. Information-Driven Modeling of Protein-Peptide Complexes
- Author
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Mikael Trellet, Alexandre M. J. J. Bonvin, and Adrien S. J. Melquiond
- Subjects
chemistry.chemical_classification ,Molecular recognition ,Molecular model ,chemistry ,Computer science ,Docking (molecular) ,Ligand ,Proteins metabolism ,Critical assessment ,Peptide ,Computational biology ,Binding site ,Small molecule - Abstract
Despite their biological importance in many regulatory processes, protein-peptide recognition mechanisms are difficult to study experimentally at the structural level because of the inherent flexibility of peptides and the often transient interactions on which they rely. Complementary methods like biomolecular docking are therefore required. The prediction of the three-dimensional structure of protein-peptide complexes raises unique challenges for computational algorithms, as exemplified by the recent introduction of protein-peptide targets in the blind international experiment CAPRI (Critical Assessment of PRedicted Interactions). Conventional protein-protein docking approaches are often struggling with the high flexibility of peptides whose short sizes impede protocols and scoring functions developed for larger interfaces. On the other side, protein-small ligand docking methods are unable to cope with the larger number of degrees of freedom in peptides compared to small molecules and the typically reduced available information to define the binding site. In this chapter, we describe a protocol to model protein-peptide complexes using the HADDOCK web server, working through a test case to illustrate every steps. The flexibility challenge that peptides represent is dealt with by combining elements of conformational selection and induced fit molecular recognition theories.
- Published
- 2014
17. Building macromolecular assemblies by information-driven docking: introducing the HADDOCK multibody docking server
- Author
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Ezgi, Karaca, Adrien S J, Melquiond, Sjoerd J, de Vries, Panagiotis L, Kastritis, and Alexandre M J J, Bonvin
- Subjects
Models, Molecular ,Internet ,User-Computer Interface ,Macromolecular Substances ,Multiprotein Complexes ,Research ,Computational Biology ,Amino Acids ,Crystallography, X-Ray - Abstract
Over the last years, large scale proteomics studies have generated a wealth of information of biomolecular complexes. Adding the structural dimension to the resulting interactomes represents a major challenge that classical structural experimental methods alone will have difficulties to confront. To meet this challenge, complementary modeling techniques such as docking are thus needed. Among the current docking methods, HADDOCK (High Ambiguity-Driven DOCKing) distinguishes itself from others by the use of experimental and/or bioinformatics data to drive the modeling process and has shown a strong performance in the critical assessment of prediction of interactions (CAPRI), a blind experiment for the prediction of interactions. Although most docking programs are limited to binary complexes, HADDOCK can deal with multiple molecules (up to six), a capability that will be required to build large macromolecular assemblies. We present here a novel web interface of HADDOCK that allows the user to dock up to six biomolecules simultaneously. This interface allows the inclusion of a large variety of both experimental and/or bioinformatics data and supports several types of cyclic and dihedral symmetries in the docking of multibody assemblies. The server was tested on a benchmark of six cases, containing five symmetric homo-oligomeric protein complexes and one symmetric protein-DNA complex. Our results reveal that, in the presence of either bioinformatics and/or experimental data, HADDOCK shows an excellent performance: in all cases, HADDOCK was able to generate good to high quality solutions and ranked them at the top, demonstrating its ability to model symmetric multicomponent assemblies. Docking methods can thus play an important role in adding the structural dimension to interactomes. However, although the current docking methodologies were successful for a vast range of cases, considering the variety and complexity of macromolecular assemblies, inclusion of some kind of experimental information (e.g. from mass spectrometry, nuclear magnetic resonance, cryoelectron microscopy, etc.) will remain highly desirable to obtain reliable results.
- Published
- 2010
18. Structures of soluble amyloid oligomers from computer simulations
- Author
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Normand Mousseau, Philippe Derreumaux, and Adrien S. J. Melquiond
- Subjects
chemistry.chemical_classification ,Amyloid ,Protein Folding ,Chemistry ,Phenylalanine ,Fibrillogenesis ,Peptide ,Amyloid fibril ,Fibril ,Biochemistry ,Protein Structure, Tertiary ,chemistry.chemical_compound ,Crystallography ,Molecular dynamics ,Monomer ,Structural Biology ,Humans ,Computer Simulation ,Critical nucleus ,Multiplicity (chemistry) ,Protein Structure, Quaternary ,Molecular Biology - Abstract
Alzheimer's, Parkinson's, and Cre- utzfeldt-Jakob's neurodegenerative diseases are all linked with the assembly of normally soluble pro- teins into amyloid fibrils. Because of experimental limitations, structural characterization of the solu- ble oligomers, which form early in the process of fibrillogenesis and are cytotoxic, remains to be determined. In this article, we study the aggregation paths of seven chains of the shortest amyloid-form- ing peptide, using an activitated method and a reduced atomic representation. Our simulations show that disordered KFFE monomers ultimately form three distinct topologies of similar energy: amorphous oligomers, incomplete rings with b-bar- rel character, and cross-b-sheet structures with the meridional but not the equatorial X-ray fiber reflec- tions. The simulations also shed light on the path- ways from misfolded aggregates to fibrillar-like structures. They also underline the multiplicity of building blocks that can lead to the formation of the critical nucleus from which rapid growth of the fibril occurs. Proteins 2006;65:180-191. V C 2006 Wiley
- Published
- 2006
19. Following the aggregation of amyloid-forming peptides by computer simulations
- Author
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Adrien S. J. Melquiond, Geneviève Boucher, Normand Mousseau, and Philippe Derreumaux
- Subjects
chemistry.chemical_classification ,Models, Molecular ,Amyloid beta-Peptides ,Binding Sites ,Amyloid ,Protein Conformation ,Molecular biophysics ,General Physics and Astronomy ,Peptide ,Amyloid fibril ,Oligomer ,Peptide Fragments ,chemistry.chemical_compound ,Sequence dependent ,chemistry ,Models, Chemical ,Computational chemistry ,Multiprotein Complexes ,Biophysics ,Computer Simulation ,Physical and Theoretical Chemistry ,Dimerization ,Macromolecule ,Protein Binding - Abstract
There is experimental evidence suggesting that the toxicity of neurodegenerative diseases such as Alzheimer’s disease may result from the soluble intermediate oligomers. It is therefore important to characterize extensively the early steps of oligomer formation at atomic level. As these structures are metastable and short lived, experimental data are difficult to obtain and they must be complemented with numerical simulations. In this work, we use the activation-relaxation technique coupled with a coarse-grained energy model to study in detail the mechanisms of aggregation of four lys‐phe‐phe‐glu ! KFFE" peptides. This is the shortest peptide known to form amyloid fibrils in vitro. Our simulations indicate that four KFFE peptides adopt a variety of oligomeric states ! tetramers, trimers, and dimers" with various orientations of the chains in rapid equilibrium. This conformational distribution is consistent with all-atom molecular-dynamics simulations in explicit solvent and is sequence dependent; as seen experimentally, the lys‐pro‐gly‐glu ! KPGE" peptides adopt disordered structures in solution. Our unbiased simulations also indicate that the assembly process is much more complex than previously thought and point to intermediate structures which likely are kinetic traps for longer chains. © 2005 American Institute of Physics. # DOI: 10.1063/1.1886725$
- Published
- 2005
20. Probing amyloid fibril formation of the NFGAIL peptide by computer simulations
- Author
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Philippe Derreumaux, Jean-Christophe Gelly, Adrien S. J. Melquiond, and Normand Mousseau
- Subjects
Models, Molecular ,chemistry.chemical_classification ,Amyloid ,Chemistry ,Dimer ,Molecular biophysics ,General Physics and Astronomy ,Peptide ,Amyloid fibril ,Protein Structure, Secondary ,Amorphous solid ,Crystallography ,chemistry.chemical_compound ,Protein structure ,medicine.anatomical_structure ,medicine ,Computer Simulation ,Physical and Theoretical Chemistry ,Peptides ,Nucleus ,Macromolecule - Abstract
Amyloid fibril formation, as observed in Alzheimer's disease and type II diabetes, is currently described by a nucleation-condensation mechanism, but the details of the process preceding the formation of the nucleus are still lacking. In this study, using an activation-relaxation technique coupled to a generic energy model, we explore the aggregation pathways of 12 chains of the hexapeptide NFGAIL. The simulations show, starting from a preformed parallel dimer and ten disordered chains, that the peptides form essentially amorphous oligomers or more rarely ordered beta-sheet structures where the peptides adopt a parallel orientation within the sheets. Comparison between the simulations indicates that a dimer is not a sufficient seed for avoiding amorphous aggregates and that there is a critical threshold in the number of connections between the chains above which exploration of amorphous aggregates is preferred.
- Published
- 2007
21. A unified conformational selection and induced fit approach to protein-peptide docking.
- Author
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Mikael Trellet, Adrien S J Melquiond, and Alexandre M J J Bonvin
- Subjects
Medicine ,Science - Abstract
Protein-peptide interactions are vital for the cell. They mediate, inhibit or serve as structural components in nearly 40% of all macromolecular interactions, and are often associated with diseases, making them interesting leads for protein drug design. In recent years, large-scale technologies have enabled exhaustive studies on the peptide recognition preferences for a number of peptide-binding domain families. Yet, the paucity of data regarding their molecular binding mechanisms together with their inherent flexibility makes the structural prediction of protein-peptide interactions very challenging. This leaves flexible docking as one of the few amenable computational techniques to model these complexes. We present here an ensemble, flexible protein-peptide docking protocol that combines conformational selection and induced fit mechanisms. Starting from an ensemble of three peptide conformations (extended, a-helix, polyproline-II), flexible docking with HADDOCK generates 79.4% of high quality models for bound/unbound and 69.4% for unbound/unbound docking when tested against the largest protein-peptide complexes benchmark dataset available to date. Conformational selection at the rigid-body docking stage successfully recovers the most relevant conformation for a given protein-peptide complex and the subsequent flexible refinement further improves the interface by up to 4.5 Å interface RMSD. Cluster-based scoring of the models results in a selection of near-native solutions in the top three for ∼75% of the successfully predicted cases. This unified conformational selection and induced fit approach to protein-peptide docking should open the route to the modeling of challenging systems such as disorder-order transitions taking place upon binding, significantly expanding the applicability limit of biomolecular interaction modeling by docking.
- Published
- 2013
- Full Text
- View/download PDF
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