19 results on '"Pim W. J. M. Frederix"'
Search Results
2. Coacervate formation studied by explicit solvent coarse-grain molecular dynamics with the Martini model
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Siewert J. Marrink, Paulo C. T. Souza, Maria Tsanai, Carsten F. E. Schroer, Pim W. J. M. Frederix, and Molecular Dynamics
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0303 health sciences ,Quantitative Biology::Biomolecules ,Coacervate ,Materials science ,02 engineering and technology ,General Chemistry ,021001 nanoscience & nanotechnology ,Force field (chemistry) ,Polyelectrolyte ,Ion ,03 medical and health sciences ,Molecular dynamics ,Chemistry ,Chemical physics ,Phase (matter) ,Molecule ,Diffusion (business) ,0210 nano-technology ,030304 developmental biology - Abstract
Complex coacervates are liquid–liquid phase separated systems, typically containing oppositely charged polyelectrolytes. They are widely studied for their functional properties as well as their potential involvement in cellular compartmentalization as biomolecular condensates. Diffusion and partitioning of solutes into a coacervate phase are important to address because their highly dynamic nature is one of their most important functional characteristics in real-world systems, but are difficult to study experimentally or even theoretically without an explicit representation of every molecule in the system. Here, we present an explicit-solvent, molecular dynamics coarse-grain model of complex coacervates, based on the Martini 3.0 force field. We demonstrate the accuracy of the model by reproducing the salt dependent coacervation of poly-lysine and poly-glutamate systems, and show the potential of the model by simulating the partitioning of ions and small nucleotides between the condensate and surrounding solvent phase. Our model paves the way for simulating coacervates and biomolecular condensates in a wide range of conditions, with near-atomic resolution., Martini 3 force field can capture the experimental trends of complex coacervates and can be extended to gain physical insight on the mechanisms that drive the formation of LLPS.
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- 2021
3. Stochastic Emergence of Two Distinct Self-Replicators from a Dynamic Combinatorial Library
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Gaël Schaeffer, Marcel J. Eleveld, Jim Ottelé, Peter C. Kroon, Pim W. J. M. Frederix, Shuo Yang, Sijbren Otto, System Chemistry, and Synthetic Organic Chemistry
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Stochastic Processes ,Colloid and Surface Chemistry ,General Chemistry ,Biochemistry ,Catalysis ,Gene Library - Abstract
Unraveling how chemistry can give rise to biology is one of the greatest challenges of contemporary science. Achieving life-like properties in chemical systems is therefore a popular topic of research. Synthetic chemical systems are usually deterministic: the outcome is determined by the experimental conditions. In contrast, many phenomena that occur in nature are not deterministic but caused by random fluctuations (stochastic). Here, we report on how, from a mixture of two synthetic molecules, two different self-replicators emerge in a stochastic fashion. Under the same experimental conditions, the two self-replicators are formed in various ratios over several repeats of the experiment. We show that this variation is caused by a stochastic nucleation process and that this stochasticity is more pronounced close to a phase boundary. While stochastic nucleation processes are common in crystal growth and chiral symmetry breaking, it is unprecedented for systems of synthetic self-replicators.
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- 2022
4. Caught in the Act: Mechanistic Insight into Supramolecular Polymerization-Driven Self-Replication from Real-Time Visualization
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Jim Ottelé, Peter C. Kroon, Wouter H. Roos, Guillermo Monreal Santiago, Omer Markovitch, Sijbren Otto, Marc C. A. Stuart, Pim W. J. M. Frederix, Sourav Maity, Siewert J. Marrink, Molecular Biophysics, System Chemistry, Polymer Science, Stratingh Institute of Chemistry, Electron Microscopy, and Molecular Dynamics
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Chemistry ,Supramolecular chemistry ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Article ,PARAMETERS ,Catalysis ,0104 chemical sciences ,Molecular dynamics ,Colloid and Surface Chemistry ,Self-replication ,Polymerization ,MOLECULAR-DYNAMICS ,SYSTEMS ,Mechanism (philosophy) ,FORCE-FIELD ,Biophysics ,Molecule ,Self-assembly ,Biophysical chemistry - Abstract
Self-assembly features prominently in fields ranging from materials science to biophysical chemistry. Assembly pathways, often passing through transient intermediates, can control the outcome of assembly processes. Yet, the mechanisms of self-assembly remain largely obscure due to a lack of experimental tools for probing these pathways at the molecular level. Here, the self-assembly of self-replicators into fibers is visualized in real-time by high-speed atomic force microscopy (HS-AFM). Fiber growth requires the conversion of precursor molecules into six-membered macrocycles, which constitute the fibers. HS-AFM experiments, supported by molecular dynamics simulations, revealed that aggregates of precursor molecules accumulate at the sides of the fibers, which then diffuse to the fiber ends where growth takes place. This mechanism of precursor reservoir formation, followed by one-dimensional diffusion, which guides the precursor molecules to the sites of growth, reduces the entropic penalty associated with colocalizing precursors and growth sites and constitutes a new mechanism for supramolecular polymerization.
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- 2020
5. Tunable Supramolecular Gel Properties by Varying Thermal History
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Sisir Debnath, Neil T. Hunt, Sangita Roy, Susana M. Ramalhete, Yaroslav Z. Khimyak, Rein V. Ulijn, Pim W. J. M. Frederix, Nadeem Javid, Andrew R. Hirst, Jesús Angulo, Yousef M. Abul-Haija, and Sharon M. Kelly
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Supramolecular chirality ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,technology, industry, and agriculture ,Stacking ,Supramolecular chemistry ,macromolecular substances ,General Chemistry ,010402 general chemistry ,01 natural sciences ,Catalysis ,0104 chemical sciences ,Hydrophobic effect ,Chemical engineering ,Self-healing hydrogels ,Peptide amphiphile ,Molecule ,QD ,Self-assembly - Abstract
The possibility of using differential pre-heating prior to supramolecular gelation to control the balance between hydrogen-bonding and aromatic stacking interactions in supramolecular gels and obtain consequent systematic regulation of structure and properties is demonstrated. Using a model aromatic peptide amphiphile, Fmoc-tyrosyl-leucine (Fmoc-YL) and a combination of fluorescence, infrared, circular dichroism and NMR spectroscopy, it is shown that the balance of these interactions can be adjusted by temporary exposure to elevated temperatures in the range 313-365 K, followed by supramolecular locking in the gel state by cooling to room temperature. Distinct regimes can be identified regarding the balance between H-bonding and aromatic stacking interactions, with a transition point at 333 K. Consequently, gels can be obtained with customizable properties, including supramolecular chirality and gel stiffness. The differential supramolecular structures also result in changes in proteolytic stability, highlighting the possibility of obtaining a range of supramolecular architectures from a single molecular structure by simply controlling the pre-assembly temperature.
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- 2019
6. Molecular simulations of self-assembling bio-inspired supramolecular systems and their connection to experiments
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Pim W. J. M. Frederix, Siewert J. Marrink, and Ilias Patmanidis
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PEPTIDE-BASED NANOSTRUCTURES ,Nanostructure ,Field (physics) ,Computer science ,Supramolecular chemistry ,Nanotechnology ,ACID SIDE-CHAINS ,Degrees of freedom (mechanics) ,010402 general chemistry ,01 natural sciences ,GENERAL FORCE-FIELD ,CIRCULAR-DICHROISM ,Software ,2D IR SPECTROSCOPY ,0103 physical sciences ,Nanobiotechnology ,COARSE-GRAINED SIMULATIONS ,Quantum ,010304 chemical physics ,DYNAMICS SIMULATIONS ,business.industry ,SHORT AMPHIPHILIC PEPTIDES ,SMALL ORGANIC-MOLECULES ,Observable ,FREE-ENERGY ,General Chemistry ,0104 chemical sciences ,Chemistry ,business - Abstract
The self-assembly of bio-inspired supramolecular polymers can be unravelled using molecular dynamics simulations combined with experiments., In bionanotechnology, the field of creating functional materials consisting of bio-inspired molecules, the function and shape of a nanostructure only appear through the assembly of many small molecules together. The large number of building blocks required to define a nanostructure combined with the many degrees of freedom in packing small molecules has long precluded molecular simulations, but recent advances in computational hardware as well as software have made classical simulations available to this strongly expanding field. Here, we review the state of the art in simulations of self-assembling bio-inspired supramolecular systems. We will first discuss progress in force fields, simulation protocols and enhanced sampling techniques using recent examples. Secondly, we will focus on efforts to enable the comparison of experimentally accessible observables and computational results. Experimental quantities that can be measured by microscopy, spectroscopy and scattering can be linked to simulation output either directly or indirectly, via quantum mechanical or semi-empirical techniques. Overall, we aim to provide an overview of the various computational approaches to understand not only the molecular architecture of nanostructures, but also the mechanism of their formation.
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- 2018
7. Structural and Spectroscopic Properties of Assemblies of Self-Replicating Peptide Macrocycles
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Siewert J. Marrink, Anna S. Bondarenko, Mathieu Surin, Thomas L. C. Jansen, Gaël Schaeffer, Yigit Altay, Julien Idé, Sijbren Otto, David Beljonne, Pim W. J. M. Frederix, Molecular Dynamics, Synthetic Organic Chemistry, and Theory of Condensed Matter
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DYNAMICS ,Circular dichroism ,spectroscopy ,Absorption spectroscopy ,PROTEINS ,Supramolecular chemistry ,General Physics and Astronomy ,Infrared spectroscopy ,Molecular Dynamics Simulation ,010402 general chemistry ,01 natural sciences ,self-replication ,Article ,Molecular dynamics ,0103 physical sciences ,nanostructures ,IMPLEMENTATION ,Molecule ,General Materials Science ,AMPHIPHILES ,Protein secondary structure ,chemistry.chemical_classification ,MOLECULAR SIMULATION ,010304 chemical physics ,Circular Dichroism ,General Engineering ,WATER MODELS ,self-assembly ,DRIVEN ,simulation ,molecular dynamics ,0104 chemical sciences ,Supramolecular polymers ,GROMOS FORCE-FIELD ,SUPRAMOLECULAR POLYMERS ,Crystallography ,chemistry ,Chemical physics ,peptides ,AMYLOID FIBRIL - Abstract
Self-replication at the molecular level is often seen as essential to the early origins of life. Recently a mechanism of self-replication has been discovered in which replicator self-assembly drives the process. We have studied one of the examples of such self-assembling self-replicating molecules to a high level of structural detail using a combination of computational and spectroscopic techniques. Molecular Dynamics simulations of self-assembled stacks of peptide-derived replicators provide insights into the structural characteristics of the system and serve as the basis for semiempirical calculations of the UV-vis, circular dichroism (CD) and infrared (IR) absorption spectra that reflect the chiral organization and peptide secondary structure of the stacks. Two proposed structural models are tested by comparing calculated spectra to experimental data from electron microscopy, CD and IR spectroscopy, resulting in a better insight into the specific supramolecular interactions that lead to self-replication. Specifically, we find a cooperative self-assembly process in which β-sheet formation leads to well-organized structures, while also the aromatic core of the macrocycles plays an important role in the stability of the resulting fibers.
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- 2017
8. Polymeric peptide pigments with sequence-encoded properties
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Hang-Ah Park, Tai-De Li, Ayala Lampel, Steven Greenbaum, Barney Yoo, Pim W. J. M. Frederix, Gary G. Scott, Rinat R. Abzalimov, Scott A. McPhee, Tell Tuttle, Sunita Humagain, Doeke R. Hekstra, Chunhua Hu, Christopher J. Bettinger, Rein V. Ulijn, and Molecular Dynamics
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Protein Conformation ,Ultraviolet Rays ,HYDROGELS ,NANOTUBES ,Peptide ,Context (language use) ,02 engineering and technology ,Tripeptide ,010402 general chemistry ,01 natural sciences ,Mass Spectrometry ,Protein structure ,Polymer chemistry ,EUMELANIN ,BIOMATERIALS ,Peptide sequence ,Chromatography, High Pressure Liquid ,chemistry.chemical_classification ,Melanins ,Multidisciplinary ,021001 nanoscience & nanotechnology ,Small molecule ,Combinatorial chemistry ,0104 chemical sciences ,QD450 ,chemistry ,Polymerization ,Covalent bond ,Tyrosine ,Protein Multimerization ,0210 nano-technology ,Peptides ,Oxidation-Reduction - Abstract
Designing molecular disorder Melanins are a group of natural pigments that are the primary factor affecting skin color. Lampel et al. examined a family of melanin-inspired materials based on tripeptides containing tyrosine as precursors for polymeric pigments. They found that the supramolecular organization of the tripeptide assembly is the most important factor for the enzymatic oxidation, with the position of the tyrosine residue playing a dominant role. Thus, simply juggling the order of the peptides allowed tuning of the optical and electrical properties of the resulting polymers. Science , this issue p. 1064
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- 2017
9. Exchange pathways of plastoquinone and plastoquinol in the photosystem II complex
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Xavier Periole, Floris J. van Eerden, Pim W. J. M. Frederix, Manuel N. Melo, Siewert J. Marrink, and Molecular Dynamics
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0301 basic medicine ,Time Factors ,photosystem II complex ,Photosystem II ,Plastoquinone ,Science ,General Physics and Astronomy ,Molecular Dynamics Simulation ,Photosynthesis ,Models, Biological ,Thylakoids ,General Biochemistry, Genetics and Molecular Biology ,Article ,Diffusion ,Electron Transport ,03 medical and health sciences ,chemistry.chemical_compound ,Molecular dynamics ,0302 clinical medicine ,Botany ,Multidisciplinary ,Cytochrome b6f complex ,platoquinone ,Photosystem II Protein Complex ,Oxidation reduction ,General Chemistry ,thylakoid membrane ,Electron transport chain ,Plant Leaves ,plastoquinol ,030104 developmental biology ,chemistry ,Thylakoid ,Biophysics ,Oxidation-Reduction ,030217 neurology & neurosurgery - Abstract
Plastoquinone (PLQ) acts as an electron carrier between photosystem II (PSII) and the cytochrome b6f complex. To understand how PLQ enters and leaves PSII, here we show results of coarse grained molecular dynamics simulations of PSII embedded in the thylakoid membrane, covering a total simulation time of more than 0.5 ms. The long time scale allows the observation of many spontaneous entries of PLQ into PSII, and the unbinding of plastoquinol (PLQol) from the complex. In addition to the two known channels, we observe a third channel for PLQ/PLQol diffusion between the thylakoid membrane and the PLQ binding sites. Our simulations point to a promiscuous diffusion mechanism in which all three channels function as entry and exit channels. The exchange cavity serves as a PLQ reservoir. Our simulations provide a direct view on the exchange of electron carriers, a key step of the photosynthesis machinery., Plastoquinone (PLQ) shuttles electrons between photosystem II (PSII) and cytochrome b6f. Here the authors perform molecular dynamics simulations and propose that PLQ enters the exchange cavity of PSII by a promiscuous diffusion mechanism whereby three different channels each act as entry and exit points.
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- 2017
10. Tunable Supramolecular Hydrogels for Selection of Lineage-Guiding Metabolites in Stem Cell Cultures
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Sangita Roy, Bruno Péault, Jingli Yang, Dimitris A. Lamprou, Nadeem Javid, Sanne C.J. Bakker, Angela Miller, Karl Burgess, Andrew J. Urquhart, Matthew J. Dalby, Scott Fleming, Christopher C. West, Ayala Lampel, Pim W. J. M. Frederix, Rein V. Ulijn, Vineetha Jayawarna, Neil T. Hunt, and Enateri V. Alakpa
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Materials science ,General Chemical Engineering ,Cellular differentiation ,Metabolite ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Chondrocyte ,chemistry.chemical_compound ,Metabolomics ,Materials Chemistry ,medicine ,Environmental Chemistry ,QD ,Biochemistry (medical) ,Osteoblast ,General Chemistry ,021001 nanoscience & nanotechnology ,Chondrogenesis ,0104 chemical sciences ,Cell biology ,medicine.anatomical_structure ,chemistry ,Self-healing hydrogels ,Stem cell ,0210 nano-technology - Abstract
Stem cells are known to differentiate in response to the chemical and mechanical properties of the substrates on which they are cultured. Thus, supramolecular biomaterials with tunable properties are well suited for the study of stem cell differentiation. In this report, we exploited this phenomenon by combining stem cell differentiation in hydrogels with variable stiffness and metabolomics analysis to identify specific bioactive lipids that are uniquely used up during differentiation. To achieve this, we cultured perivascular stem cells on supramolecular peptide gels of different stiffness, and metabolite depletion followed. On soft (1 kPa), stiff (13 kPa), and rigid (32 kPa) gels, we observed neuronal, chondrogenic, and osteogenic differentiation, respectively, showing that these stem cells undergo stiffness-directed fate selection. By analyzing concentration variances of >600 metabolites during differentiation on the stiff and rigid gels (and focusing on chondrogenesis and osteogenesis as regenerative targets, respectively), we identified that specific lipids (lysophosphatidic acid and cholesterol sulfate, respectively), were significantly depleted. We propose that these metabolites are therefore involved in the differentiation process. In order to unequivocally demonstrate that the lipid metabolites that we identified play key roles in driving differentiation, we subsequently demonstrated that these individual lipids can, when fed to standard stem cell cultures, induce differentiation toward chondrocyte and osteoblast phenotypes. Our concept exploits the design of supramolecular biomaterials as a strategy for discovering cell-directing bioactive metabolites of therapeutic relevance.
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- 2016
11. Prediction of Thylakoid Lipid Binding Sites on Photosystem II
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Pim W. J. M. Frederix, Floris J. van Eerden, Siewert J. Marrink, Manuel N. Melo, and Molecular Dynamics
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Glycerol ,0301 basic medicine ,MOLECULAR-DYNAMICS SIMULATIONS ,Photosystem II ,Protein Conformation ,Membrane lipids ,Biophysics ,Plastoquinone ,Molecular Dynamics Simulation ,Photosynthesis ,Thylakoids ,Sulfoquinovosyl diacylglycerol ,CHLAMYDOMONAS-REINHARDTII ,Light-harvesting complex ,Membrane Lipids ,03 medical and health sciences ,chemistry.chemical_compound ,Journal Article ,ELECTRON-TRANSPORT ,LIGHT-HARVESTING COMPLEX ,Binding Sites ,MEMBRANE-PROTEINS ,DIGALACTOSYL-DIACYLGLYCEROL ,Photosystem II Protein Complex ,Proteins ,food and beverages ,Galactolipids ,SULFOQUINOVOSYL DIACYLGLYCEROL ,PROTEIN INTERACTIONS ,030104 developmental biology ,chemistry ,Thylakoid ,ARABIDOPSIS-THALIANA ,lipids (amino acids, peptides, and proteins) ,MARTINI FORCE-FIELD ,Protein Binding - Abstract
The thylakoid membrane has a unique lipid composition, consisting mostly of galactolipids. These thylakoid lipids have important roles in photosynthesis. Here, we investigate to what extent these lipids bind specifically to the Photosystem II complex. To this end, we performed coarse-grain MD simulations of the Photosystem II complex embedded in a thylakoid membrane with realistic composition. Based on >85 μs simulation time, we find that monogalactosyldiacylglycerol and sulfoquinovosyldiacylglycerol lipids are enriched in the annular shell around the protein, and form distinct binding sites. From the analysis of residue contacts, we conclude that electrostatic interactions play an important role in stabilizing these binding sites. Furthermore, we find that chlorophyll a has a prevalent role in the coordination of the lipids. In addition, we observe lipids to diffuse in and out of the plastoquinone exchange cavities, allowing exchange of cocrystallized lipids with the bulk membrane and suggesting a more open nature of the plastoquinone exchange cavity. Together, our data provide a wealth of information on protein-lipid interactions for a key protein in photosynthesis.
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- 2017
12. Transient supramolecular reconfiguration of peptide nanostructures using ultrasound
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Sisir Debnath, Pim W. J. M. Frederix, Charalampos G. Pappas, Shuo Bia, Rein V. Ulijn, Anthony Gachagan, Scott Fleming, Sharon M. Kelly, and Tapiwa Mutasa
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Nanostructure ,Materials science ,Process Chemistry and Technology ,Supramolecular chemistry ,Control reconfiguration ,Nanotechnology ,Fluorescence ,QD450 ,Mechanics of Materials ,Amphiphile ,Biophysics ,General Materials Science ,Transient (oscillation) ,Electrical and Electronic Engineering ,Dissolution ,Ultrasound energy - Abstract
Ultrasound, i.e. high frequency oscillating pressure waves, is commonly used to overcome kinetic barriers associated with dissolution, assembly and gelation.We demonstrate that ultrasound energy may also be used to achieve transient reorganization of supramolecular nanostructures, which revert back to the original state when sound is switched off. Aromatic peptide amphiphiles, Fmoc-FL and -YL were used to study the transient acoustic response. These systems showed temporary supramolecular transitions that were sequence dependent. The changes observed were due to an altered balance between H-bonding and p-stacking, giving rise in changes in chiral organisation of peptide building blocks. Transient reconfiguration was visualized by TEM and changes in supramolecular interactions characterized by fluorescence, FT-IR and CD. Remarkably, significant differences are observed when compared to thermal heating, which shows relates to the oscillating and directional characteristics of ultrasound when delivering heat to a system.
- Published
- 2015
13. Conducting Nanofibers and Organogels Derived from the Self-Assembly of Tetrathiafulvalene-Appended Dipeptides
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Alexander L. Kanibolotsky, Helena Gleskova, Mischa Zelzer, Nadezhda Shivarova, Swati Gupta, Peter J. Skabara, Rein V. Ulijn, Siva Krishna Mohan Nalluri, and Pim W. J. M. Frederix
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TP ,Materials science ,TK ,Nanofibers ,Ethyl acetate ,chemistry.chemical_compound ,Heterocyclic Compounds ,Polymer chemistry ,Electrochemistry ,Moiety ,Organic chemistry ,General Materials Science ,Fourier transform infrared spectroscopy ,Diphenylalanine ,Spectroscopy ,chemistry.chemical_classification ,Molecular Structure ,technology, industry, and agriculture ,Dipeptides ,Surfaces and Interfaces ,Electron acceptor ,Condensed Matter Physics ,QD450 ,chemistry ,Nanofiber ,Cyclic voltammetry ,Gels ,Tetrathiafulvalene - Abstract
In this article, we demonstrate the non-aqueous self-assembly of a low-molecular-mass organic gelator based on an electroactive p-type tetrathiafulvalene (TTF)-dipeptide bioconjugate. We show that a TTF moiety appended with diphenylalanine amide derivative (TTF-FF-NH2) self-assembles into one-dimensional nanofibers that further lead to the formation of self-supporting organogels in chloroform and ethyl acetate. Upon doping of the gels with electron acceptors (TCNQ/iodine vapor), stable two-component charge transfer gels are produced in chloroform and ethyl acetate. These gels are characterized by various spectroscopy (UV-vis-NIR, FTIR and CD), microscopy (AFM and TEM), rheology and cyclic voltammetry techniques. Furthermore, conductivity measurements performed on TTF-FF-NH2 xerogel nanofiber networks formed between gold electrodes on a glass surface indicate that these nanofibers show a remarkable enhancement in the conductivity after doping with TCNQ.
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- 2014
14. Role of Charge and Hydrophobicity in Liprotide Formation: A Molecular Dynamics Study with Experimental Constraints
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Pim W. J. M. Frederix, Jan Skov Pedersen, Jannik Nedergaard Pedersen, Siewert J. Marrink, Daniel E. Otzen, and Molecular Dynamics
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0301 basic medicine ,TUMOR-CELLS ,Calorimetry ,Molecular Dynamics Simulation ,01 natural sciences ,Biochemistry ,Protein–protein interaction ,Hydrophobic effect ,03 medical and health sciences ,Molecular dynamics ,X-Ray Diffraction ,0103 physical sciences ,Scattering, Small Angle ,Journal Article ,Molecular Biology ,MOLTEN GLOBULE ,010304 chemical physics ,biology ,FATTY-ACID ,Chemistry ,Small-angle X-ray scattering ,Organic Chemistry ,HUMAN ALPHA-LACTALBUMIN ,Isothermal titration calorimetry ,OLEIC-ACID ,Molten globule ,X-RAY-SCATTERING ,PROTEIN INTERACTIONS ,Crystallography ,030104 developmental biology ,Alpha-lactalbumin ,biology.protein ,FORCE-FIELD ,Lactalbumin ,Molecular Medicine ,COMPLEXES ,Lipid core ,HAMLET ,Hydrophobic and Hydrophilic Interactions ,Oleic Acid - Abstract
Bovine α-lactalbumin (aLA) and oleate (OA) form a complex that has been intensively studied for its tumoricidal activity. Small-angle X-ray scattering (SAXS) has revealed that this complex consists of a lipid core surrounded by partially unfolded protein. We call this type of complex a liprotide. Little is known of the molecular interactions between OA and aLA, and no technique has so far provided any high-resolution structure of a liprotide. Here we have used coarse-grained (CG) molecular dynamics (MD) simulations, isothermal titration calorimetry (ITC) and SAXS to investigate the interactions between aLA and OA during the process of liprotide formation. With ITC we found that the strongest enthalpic interactions occurred at a molar ratio of 12.0±1.4:1 OA/aLA. Liprotides formed between OA and aLA at several OA/aLA ratios in silico were stable both in CG and in all-atom simulations. From the simulated structures we calculated SAXS spectra that show good agreement with experimentally measured patterns of matching liprotides. The simulations showed that aLA assumes a molten globular (MG) state, exposing several hydrophobic patches involved in interactions with OA. Initial binding of aLA to OA occurs in an area of aLA in which a high amount of positive charge is located, and only later do hydrophobic interactions become important. The results reveal how unfolding of aLA to expose hydrophobic residues is important for complex formation between aLA and OA. Our findings suggest a general mechanism for liprotide formation and might explain the ability of a large number of proteins to form liprotides with OA.
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- 2017
15. Molecular Dynamics of Photosystem II Embedded in the Thylakoid Membrane
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Pim W. J. M. Frederix, Floris J. van Eerden, Djurre H. de Jong, Xavier Periole, Tomas E. van den Berg, Siewert J. Marrink, Molecular Dynamics, Biophysics Photosynthesis/Energy, and LaserLaB - Energy
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0301 basic medicine ,Photosystem II ,Chemistry ,Protein subunit ,Dimer ,Photosystem II Protein Complex ,food and beverages ,macromolecular substances ,Molecular Dynamics Simulation ,Photosynthesis ,Thylakoids ,Surfaces, Coatings and Films ,03 medical and health sciences ,chemistry.chemical_compound ,Molecular dynamics ,Crystallography ,030104 developmental biology ,Monomer ,Membrane ,Energy Transfer ,Thylakoid ,Materials Chemistry ,SDG 7 - Affordable and Clean Energy ,Physical and Theoretical Chemistry - Abstract
Photosystem II (PSII) is one of the key protein complexes in photosynthesis. We introduce a coarse grained model of PSII and present the analysis of 60 µs molecular dynamics simulations of PSII in both monomeric and dimeric form, embedded in a thylakoid membrane model that reflects its native lipid composition. We describe in detail the setup of the protein complex and the many natural cofactors, and characterize their mobility. Overall we find that the protein subunits and cofactors are more flexible towards the periphery of the complex, as well as near the PLQ exchange cavity and at the dimer interface. Of all cofactors, β-carotenes show the highest mobility. Some of the β-carotenes diffuse in and out of the protein complex via the thylakoid membrane. In contrast to the PSII dimer, the monomeric form adopts a tilted conformation in the membrane, with strong interactions between the soluble PsbO subunit and the glycolipid headgroups. Interestingly, the tilted conformation causes buckling of the membrane. Together, our results provide an unprecedented view of PSII dynamics on a microsecond time scale. Our data may be used as basis for the interpretation of experimental data as well as for theoretical models describing exciton energy transfer.
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- 2017
16. Alignment of nanostructured tripeptide gels by directional ultrasonication
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Charalampos G. Pappas, Shuo Bai, Pim W. J. M. Frederix, Rein V. Ulijn, Scott Fleming, Yousef M. Abul-Haija, Sharon M. Kelly, Tapiwa Mutasa, Daniela Kalafatovic, Jacob Trevino, and Anthony Gachagan
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Circular dichroism ,Materials science ,Magnetic Resonance Spectroscopy ,Sonication ,Supramolecular chemistry ,Tripeptide ,Catalysis ,Quantitative Biology::Subcellular Processes ,Peptides, Self-assembly, Ultrasound ,Microscopy, Electron, Transmission ,Microscopy ,Spectroscopy, Fourier Transform Infrared ,Materials Chemistry ,QD ,Physics::Biological Physics ,Quantitative Biology::Biomolecules ,Circular Dichroism ,Metals and Alloys ,Hydrogels ,General Chemistry ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Nanostructures ,Condensed Matter::Soft Condensed Matter ,Crystallography ,Chemical engineering ,Self-healing hydrogels ,Ceramics and Composites ,Microscopy, Electron, Scanning ,Ultrasonic sensor ,Chirality (chemistry) ,Oligopeptides - Abstract
We demonstrate an in-situ ultrasonic approach to influence self-assembly across the supramolecular to micron length scales, showing enhancement of supramolecular interactions, chirality and orientation, which depends on the peptide sequence and solvent environment. This is the first successful demonstration of using oscillating pressure waves to generate anisotropic organo- and hydro- gels consisting of oriented tripeptides structures.
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- 2015
17. Investigation of the ultrafast dynamics occurring during unsensitized photocatalytic H2 evolution by an [FeFe]-hydrogenase subsite analogue
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Katrin Adamczyk, Christopher J. Pickett, Neil T. Hunt, Pim W. J. M. Frederix, Tell Tuttle, Joseph A. Wright, and Rein V. Ulijn
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Photohydrogen ,Hydrogenase ,Hydrogen ,Chemistry ,Organic Chemistry ,chemistry.chemical_element ,Solar fuel ,Photochemistry ,Inorganic Chemistry ,Vibrational energy relaxation ,Molecule ,Density functional theory ,Physical and Theoretical Chemistry ,QC ,Hydrogen production - Abstract
Biomimetic compounds based upon the active subsite of the [FeFe]-hydrogenase enzyme system have been the focus of much attention as catalysts for hydrogen production: a clean energy vector. Until recently, use of hydrogenase subsite systems for light-driven hydrogen production has typically required the involvement of a photosensitizer, but the molecule [(μ-pdt)(μ-H)Fe2(CO)4(dppv)]+, (1; dppv = cis-1,2-C2H2(PPh2)2; pdt = 1,3-propanedithiolate) has been reported to catalyze the evolution of hydrogen gas under sensitizer-free conditions. Establishing the molecular mechanism that leads to photohydrogen production by 1 is thus an important step that may enable further development of this family of molecules as solar fuel platforms. Here, we report ultrafast UVpump–IRprobe spectroscopy of 1 at three different excitation wavelengths and in a range of solvents, including under the conditions required for H2 production. Combining spectroscopic measurements of the photochemistry and vibrational relaxation dynamics of 1 with ground-state density functional theory (DFT) calculations shows that, irrespective of experimental conditions, near-instantaneous carbonyl ligand loss is the main photochemical channel. No evidence for a long-lived excited electronic state was found. These results provide the first time-resolved data for the photochemistry of 1 and offer an alternative interpretation of the underlying mechanism of light-driven hydrogen generation.
- Published
- 2014
18. Tuneable Fmoc–Phe–(4-X)–Phe–NH2 nanostructures by variable electronic substitution
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Pim W. J. M. Frederix, Charalampos G. Pappas, Yousef M. Abul-Haija, Angela Flack, and Rein V. Ulijn
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Nanostructure ,Stereochemistry ,Chemistry ,Condensation ,Metals and Alloys ,Supramolecular chemistry ,Beta sheet ,General Chemistry ,Catalysis ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Nanomaterials ,Crystallography ,Self-healing hydrogels ,Materials Chemistry ,Ceramics and Composites ,Polar effect ,QD ,Nanoscopic scale - Abstract
Supramolecular structures were produced by in situ enzymatic condensation of Fmoc–Phe–(4-X), where X denotes electron withdrawing or donating groups, with Phe–NH2. The relative contribution of π-stacking and H-bonding interactions can be regulated by the nature of X, resulting in tuneable nanoscale morphologies.
- Published
- 2014
19. Multidimensional infrared spectroscopy reveals the vibrational and solvation dynamics of isoniazid
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Gregory M. Greetham, Pim W. J. M. Frederix, Anthony W. Parker, Daniel J. Shaw, Michael Towrie, Neil T. Hunt, Katrin Adamczyk, Kirsty Robb, Paul A. Hoskisson, and Niall Simpson
- Subjects
Molecular Structure ,Spectrophotometry, Infrared ,Infrared ,Chemistry ,Molecular biophysics ,Solvation ,General Physics and Astronomy ,Infrared spectroscopy ,Context (language use) ,bacterial infections and mycoses ,Vibration ,QD450 ,Solubility ,Computational chemistry ,Molecular vibration ,Isoniazid ,Vibrational energy relaxation ,Quantum Theory ,Physical and Theoretical Chemistry ,Spectroscopy - Abstract
The results of infrared spectroscopic investigations into the band assignments, vibrational relaxation, and solvation dynamics of the common anti-tuberculosis treatment Isoniazid (INH) are reported. INH is known to inhibit InhA, a 2-trans-enoyl-acyl carrier protein reductase enzyme responsible for the maintenance of cell walls in Mycobacterium tuberculosis but as new drug-resistant strains of the bacterium appear, next-generation therapeutics will be essential to combat the rise of the disease. Small molecules such as INH offer the potential for use as a biomolecular marker through which ultrafast multidimensional spectroscopies can probe drug binding and so inform design strategies but a complete characterization of the spectroscopy and dynamics of INH in solution is required to inform such activity. Infrared absorption spectroscopy, in combination with density functional theory calculations, is used to assign the vibrational modes of INH in the 1400-1700 cm(-1) region of the infrared spectrum while ultrafast multidimensional spectroscopy measurements determine the vibrational relaxation dynamics and the effects of solvation via spectral diffusion of the carbonyl stretching vibrational mode. These results are discussed in the context of previous linear spectroscopy studies on solid-phase INH and its usefulness as a biomolecular probe.
- Published
- 2015
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