Search

Your search keyword '"Wiewiora, Rafal P."' showing total 22 results
Start Over Author "Wiewiora, Rafal P."
22 results on '"Wiewiora, Rafal P."'

1. Machine learning force fields and coarse-grained variables in molecular dynamics: application to materials and biological systems

Author

Gkeka, Paraskevi, Stoltz, Gabriel, Farimani, Amir Barati, Belkacemi, Zineb, Ceriotti, Michele, Chodera, John, Dinner, Aaron R., Ferguson, Andrew, Maillet, Jean-Bernard, Minoux, Hervé, Peter, Christine, Pietrucci, Fabio, Silveira, Ana, Tkatchenko, Alexandre, Trstanova, Zofia, Wiewiora, Rafal, and Leliévre, Tony

Subjects
Physics - Computational Physics, Quantitative Biology - Biomolecules
Abstract

Machine learning encompasses a set of tools and algorithms which are now becoming popular in almost all scientific and technological fields. This is true for molecular dynamics as well, where machine learning offers promises of extracting valuable information from the enormous amounts of data generated by simulation of complex systems. We provide here a review of our current understanding of goals, benefits, and limitations of machine learning techniques for computational studies on atomistic systems, focusing on the construction of empirical force fields from ab-initio databases and the determination of reaction coordinates for free energy computation and enhanced sampling.

Published
2020

3. Predicting the structural basis of targeted protein degradation by integrating molecular dynamics simulations with structural mass spectrometry

Author

Dixon, Tom, MacPherson, Derek, Mostofian, Barmak, Dauzhenka, Taras, Lotz, Samuel, McGee, Dwight, Shechter, Sharon, Shrestha, Utsab R., Wiewiora, Rafal, McDargh, Zachary A., Pei, Fen, Pal, Rajat, Ribeiro, João V., Wilkerson, Tanner, Sachdeva, Vipin, Gao, Ning, Jain, Shourya, Sparks, Samuel, Li, Yunxing, Vinitsky, Alexander, Zhang, Xin, Razavi, Asghar M., Kolossváry, István, Imbriglio, Jason, Evdokimov, Artem, Bergeron, Louise, Zhou, Wenchang, Adhikari, Jagat, Ruprecht, Benjamin, Dickson, Alex, Xu, Huafeng, Sherman, Woody, and Izaguirre, Jesus A.

Published
2022
Full Text
View/download PDF

4. OpenMM 7: Rapid development of high performance algorithms for molecular dynamics.

Author

Eastman, Peter, Swails, Jason, Chodera, John D, McGibbon, Robert T, Zhao, Yutong, Beauchamp, Kyle A, Wang, Lee-Ping, Simmonett, Andrew C, Harrigan, Matthew P, Stern, Chaya D, Wiewiora, Rafal P, Brooks, Bernard R, and Pande, Vijay S

Subjects
Computational Biology, Algorithms, Software, Molecular Dynamics Simulation, Mathematical Sciences, Biological Sciences, Information and Computing Sciences, Bioinformatics
Abstract

OpenMM is a molecular dynamics simulation toolkit with a unique focus on extensibility. It allows users to easily add new features, including forces with novel functional forms, new integration algorithms, and new simulation protocols. Those features automatically work on all supported hardware types (including both CPUs and GPUs) and perform well on all of them. In many cases they require minimal coding, just a mathematical description of the desired function. They also require no modification to OpenMM itself and can be distributed independently of OpenMM. This makes it an ideal tool for researchers developing new simulation methods, and also allows those new methods to be immediately available to the larger community.

Published
2017

5. Non-Markovian Dynamic Models Identify Non-Canonical KRAS-VHL Encounter Complex Conformations for Novel PROTAC Design

Author

Qiu, Yunrui, Wiewiora, Rafal P., Izaguirre, Jesus A., Xu, Huafeng, Sherman, Woody, Tang, Weiping, and Huang, Xuhui

Abstract

Targeted protein degradation (TPD) is emerging as a promising therapeutic approach for cancer and other diseases, with an increasing number of programs demonstrating its efficacy in human clinical trials. One notable method for TPD is Proteolysis Targeting Chimeras (PROTACs) that selectively degrade a protein of interest (POI) through E3-ligase induced ubiquitination followed by proteasomal degradation. PROTACs utilize a warhead-linker-ligand architecture to bring the POI (bound to the warhead) and the E3 ligase (bound to the ligand) into proximity. The resulting non-native protein–protein interactions (PPIs) formed between the POI and E3 ligase lead to the formation of a stable ternary complex, enhancing cooperativity for TPD. A significant challenge in PROTAC design is the screening of the linkers to induce favorable non-native PPIs between POI and E3 ligase. Here, we present a physics-based computational protocol to predict noncanonical and metastable PPI interfaces between an E3 ligase and a given POI, aiding in the design of linkers to stabilize the ternary complex and enhance degradation. Specifically, we build the non-Markovian dynamic model using the Integrative Generalized Master equation (IGME) method from ∼1.5 ms all-atom molecular dynamics simulations of linker-less encounter complex, to systematically explore the inherent PPIs between the oncogene homologue protein and the von Hippel-Lindau E3 ligase. Our protocol revealed six metastable states each containing a different PPI interface. We selected three of these metastable states containing promising PPIs for linker design. Our selection criterion included thermodynamic and kinetic stabilities of PPIs and the accessibility between the solvent-exposed sites on the warheads and E3 ligand. One selected PPIs closely matches a recent cocrystal PPI interface structure induced by an experimentally designed PROTAC with potent degradation efficacy. We anticipate that our protocol has significant potential for widespread application in predicting metastable POI-ligase interfaces that can enable rational design of PROTACs.

Published
2024
Full Text
View/download PDF

6. SARS-CoV-2 simulations go exascale to predict dramatic spike opening and cryptic pockets across the proteome

Author

Zimmerman, Maxwell I., Porter, Justin R., Ward, Michael D., Singh, Sukrit, Vithani, Neha, Meller, Artur, Mallimadugula, Upasana L., Kuhn, Catherine E., Borowsky, Jonathan H., Wiewiora, Rafal P., Hurley, Matthew F. D., Harbison, Aoife M., Fogarty, Carl A., Coffland, Joseph E., Fadda, Elisa, Voelz, Vincent A., Chodera, John D., and Bowman, Gregory R.

Published
2021
Full Text
View/download PDF

9. SARS-CoV-2 Simulations Go Exascale to Capture Spike Opening and Reveal Cryptic Pockets Across the Proteome

Author

Zimmerman, Maxwell I., Porter, Justin R., Ward, Michael D., Singh, Sukrit, Vithani, Neha, Meller, Artur, Mallimadugula, Upasana L., Kuhn, Catherine E., Borowsky, Jonathan H., Wiewiora, Rafal P., Hurley, Matthew F. D., Harbison, Aoife M, Fogarty, Carl A, Coffland, Joseph E., Fadda, Elisa, Voelz, Vincent A., Chodera, John D., Bowman, Gregory R., Zimmerman, Maxwell I., Porter, Justin R., Ward, Michael D., Singh, Sukrit, Vithani, Neha, Meller, Artur, Mallimadugula, Upasana L., Kuhn, Catherine E., Borowsky, Jonathan H., Wiewiora, Rafal P., Hurley, Matthew F. D., Harbison, Aoife M, Fogarty, Carl A, Coffland, Joseph E., Fadda, Elisa, Voelz, Vincent A., Chodera, John D., and Bowman, Gregory R.

Abstract

SARS-CoV-2 has intricate mechanisms for initiating infection, immune evasion/suppression, and replication, which depend on the structure and dynamics of its constituent proteins. Many protein structures have been solved, but far less is known about their relevant conformational changes. To address this challenge, over a million citizen scientists banded together through the Folding@home distributed computing project to create the first exascale computer and simulate an unprecedented 0.1 seconds of the viral proteome. Our simulations capture dramatic opening of the apo Spike complex, far beyond that seen experimentally, which explains and successfully predicts the existence of ‘cryptic’ epitopes. Different Spike homologues modulate the probabilities of open versus closed structures, balancing receptor binding and immune evasion. We also observe dramatic conformational changes across the proteome, which reveal over 50 ‘cryptic’ pockets that expand targeting options for the design of antivirals. All data and models are freely available online, providing a quantitative structural atlas.

Published
2020

11. SARS-CoV-2 Simulations Go Exascale to Capture Spike Opening and Reveal Cryptic Pockets Across the Proteome

Author

Zimmerman, Maxwell I., primary, Porter, Justin R., additional, Ward, Michael D., additional, Singh, Sukrit, additional, Vithani, Neha, additional, Meller, Artur, additional, Mallimadugula, Upasana L., additional, Kuhn, Catherine E., additional, Borowsky, Jonathan H., additional, Wiewiora, Rafal P., additional, Hurley, Matthew F. D., additional, Harbison, Aoife M, additional, Fogarty, Carl A, additional, Coffland, Joseph E., additional, Fadda, Elisa, additional, Voelz, Vincent A., additional, Chodera, John D., additional, and Bowman, Gregory R., additional

Published
2020
Full Text
View/download PDF

13. The dynamic conformational landscape of the protein methyltransferase SETD8

Author

Chen, Shi, primary, Wiewiora, Rafal P, additional, Meng, Fanwang, additional, Babault, Nicolas, additional, Ma, Anqi, additional, Yu, Wenyu, additional, Qian, Kun, additional, Hu, Hao, additional, Zou, Hua, additional, Wang, Junyi, additional, Fan, Shijie, additional, Blum, Gil, additional, Pittella-Silva, Fabio, additional, Beauchamp, Kyle A, additional, Tempel, Wolfram, additional, Jiang, Hualiang, additional, Chen, Kaixian, additional, Skene, Robert J, additional, Zheng, Yujun George, additional, Brown, Peter J, additional, Jin, Jian, additional, Luo, Cheng, additional, Chodera, John D, additional, and Luo, Minkui, additional

Published
2019
Full Text
View/download PDF

14. Author response: The dynamic conformational landscape of the protein methyltransferase SETD8

Author

Chen, Shi, primary, Wiewiora, Rafal P, additional, Meng, Fanwang, additional, Babault, Nicolas, additional, Ma, Anqi, additional, Yu, Wenyu, additional, Qian, Kun, additional, Hu, Hao, additional, Zou, Hua, additional, Wang, Junyi, additional, Fan, Shijie, additional, Blum, Gil, additional, Pittella-Silva, Fabio, additional, Beauchamp, Kyle A, additional, Tempel, Wolfram, additional, Jiang, Hualiang, additional, Chen, Kaixian, additional, Skene, Robert J, additional, Zheng, Yujun George, additional, Brown, Peter J, additional, Jin, Jian, additional, Luo, Cheng, additional, Chodera, John D, additional, and Luo, Minkui, additional

Published
2019
Full Text
View/download PDF

18. The Dynamic Conformational Landscapes of the Protein Methyltransferase SETD8

Author

Chen, Shi, primary, Wiewiora, Rafal P., additional, Meng, Fanwang, additional, Babault, Nicolas, additional, Ma, Anqi, additional, Yu, Wenyu, additional, Qian, Kun, additional, Hu, Hao, additional, Zou, Hua, additional, Wang, Junyi, additional, Fan, Shijie, additional, Blum, Gil, additional, Pittella-Silva, Fabio, additional, Beauchamp, Kyle A., additional, Tempel, Wolfram, additional, Jiang, Hualiang, additional, Chen, Kaixian, additional, Skene, Robert, additional, Zheng, Y. George, additional, Brown, Peter J., additional, Jin, Jian, additional, Luo, Cheng, additional, Chodera, John D., additional, and Luo, Minkui, additional

Published
2018
Full Text
View/download PDF

21. OpenMM 7: Rapid Development of High Performance Algorithms for Molecular Dynamics

Author

Eastman, Peter, primary, Swails, Jason, additional, Chodera, John D., additional, McGibbon, Robert T., additional, Zhao, Yutong, additional, Beauchamp, Kyle A., additional, Wang, Lee-Ping, additional, Simmonett, Andrew C., additional, Harrigan, Matthew P., additional, Stern, Chaya D., additional, Wiewiora, Rafal P., additional, Brooks, Bernard R., additional, and Pande, Vijay S., additional

Published
2016
Full Text
View/download PDF

22. SARS-CoV-2 Simulations Go Exascale to Capture Spike Opening and Reveal Cryptic Pockets Across the Proteome.

Author

Zimmerman MI, Porter JR, Ward MD, Singh S, Vithani N, Meller A, Mallimadugula UL, Kuhn CE, Borowsky JH, Wiewiora RP, Hurley MFD, Harbison AM, Fogarty CA, Coffland JE, Fadda E, Voelz VA, Chodera JD, and Bowman GR

Abstract

SARS-CoV-2 has intricate mechanisms for initiating infection, immune evasion/suppression, and replication, which depend on the structure and dynamics of its constituent proteins. Many protein structures have been solved, but far less is known about their relevant conformational changes. To address this challenge, over a million citizen scientists banded together through the Folding@home distributed computing project to create the first exascale computer and simulate an unprecedented 0.1 seconds of the viral proteome. Our simulations capture dramatic opening of the apo Spike complex, far beyond that seen experimentally, which explains and successfully predicts the existence of 'cryptic' epitopes. Different Spike homologues modulate the probabilities of open versus closed structures, balancing receptor binding and immune evasion. We also observe dramatic conformational changes across the proteome, which reveal over 50 'cryptic' pockets that expand targeting options for the design of antivirals. All data and models are freely available online, providing a quantitative structural atlas.

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results