A5064872574- Protein Structure and Dynamics
- Lipid Membrane Structure and Behavior
- Computational Drug Discovery Methods
- Parallel Computing and Optimization Techniques
- Distributed and Parallel Computing Systems
- Digital Imaging for Blood Diseases
- Machine Learning in Bioinformatics
- Enzyme Structure and Function
- Radiomics and Machine Learning in Medical Imaging
- Force Microscopy Techniques and Applications
- Nanopore and Nanochannel Transport Studies
- Algorithms and Data Compression
- Cardiomyopathy and Myosin Studies
- AI in cancer detection
- Genetic Neurodegenerative Diseases
- Erythrocyte Function and Pathophysiology
- Advanced NMR Techniques and Applications
- Axon Guidance and Neuronal Signaling
- Cellular transport and secretion
- Genetics, Bioinformatics, and Biomedical Research
- Robotics and Automated Systems
- Robotics and Sensor-Based Localization
- Electron Spin Resonance Studies
- Plant nutrient uptake and metabolism
- Image Retrieval and Classification Techniques
Mucolipidosis IV Foundation
2025
University of Oxford
2010-2021
National Institutes of Health
2016-2020
National Institute of Diabetes and Digestive and Kidney Diseases
2016-2020
University of Groningen
2011
MDAnalysis (http://mdanalysis.org) is a library for structural and temporal analysis of molecular dynamics (MD) simulation trajectories individual protein structures. MD simulations biological molecules have become an important tool to elucidate the relationship between structure physiological function. Simulations are performed with highly optimized software packages on HPC resources but most codes generate output in their own formats so that development new trajectory algorithms confined...
Potential of mean force (PMF) calculations are used to characterize the free energy landscape protein–lipid and protein–protein association within membranes. Coarse-grained simulations allow binding energies be determined with reasonable statistical error. This accuracy relies on defining a good collective variable describe unbinding transitions, upon criteria for assessing convergence simulation toward representative equilibrium sampling. As examples, we calculate PMFs ANT/cardiolipin...
The exchange of ADP and ATP across the inner mitochondrial membrane is a fundamental cellular process. This facilitated by adenine nucleotide translocase, structure function which are critically dependent on signature phospholipid mitochondria, cardiolipin (CL). Here we employ multiscale molecular dynamics simulations to investigate CL interactions within environment. Using at both coarse-grained atomistic resolutions, identify three binding sites in agreement with those seen crystal...
Association of peripheral proteins with lipid bilayers regulates membrane signaling and dynamics. Pleckstrin homology (PH) domains bind to phosphatidylinositol phosphate (PIP) molecules in membranes. The effects local PIP enrichment on the interaction PH membranes is unclear. Molecular dynamics simulations allow estimation binding energy GRP1 domain
Atomistic simulations have recently been shown to be sufficiently accurate reversibly fold globular proteins and provided insights into folding mechanisms. Gaining similar understanding from of membrane protein association would great medical interest. All-atom the assembly transmembrane domains are much more challenging, not least due very slow diffusion within lipid bilayer membrane. Here, we focus on a simple well-characterized prototype assembly, namely dimerization glycophorin A,...
Highlights•Molecular simulations unravel how EphA2 kinase interacts with PIP2 in membranes•The juxtamembrane (JM) domain the and membrane•The JM domains drive formation of nanoclusters membrane•An integrative model supports trans autophosphorylation within clustered EphA2sSummaryEphA2 is a member receptor tyrosine family. Interactions cytoplasmic region cell membrane are functionally important yet remain incompletely characterized. Molecular dynamics combined biochemical studies reveal...
Small-molecule lead optimisation in early-stage drug discovery is broadly supported by computational chemistry approaches throughout industry. Over the last decade, Free Energy Perturbation (FEP) has grown into a mature physics-based tool that prospectively guides medicinal decision-making accurately predicting ligand potencies at level of precision required for granular nature stage. Machine-learned ligand-protein co-folding models are forefront accurate protein structure prediction and...
Small-molecule lead optimisation in early-stage drug discovery is broadly supported by computational chemistry approaches throughout industry. Over the last decade, Free Energy Perturbation (FEP) has grown into a mature physics-based tool that prospectively guides medicinal decision-making accurately predicting ligand potencies at level of precision required for granular nature stage. Machine-learned ligand-protein co-folding models are forefront accurate protein structure prediction and...
Abstract Summary Ligandbook is a public database and archive for force field parameters of small drug-like molecules. It repository parameter sets that are part published work but not easily available to the community otherwise. Parameter can be downloaded immediately used in molecular dynamics simulations. The versioned with full histories carry unique identifiers facilitate reproducible research. Text-based search on rich metadata chemical substructure allow precise identification desired...
Transmembrane helix association is a fundamental step in the folding of helical membrane proteins. The prototypical example this formation glycophorin dimer. While its structure and stability have been well-characterized experimentally, detailed assembly mechanism harder to obtain. Here, we use all-atom simulations within phospholipid study association. We find that initial results non-native intermediate, separated by significant free energy barrier from dimer with native binding interface....