AIMC Topic: Molecular Dynamics Simulation

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Mechanistic Basis for GPCR Phosphorylation-Dependent Allosteric Signaling Specificity of β-Arrestin 1 and 2.

Journal of chemical information and modeling
β-Arrestins (βarr1 and βarr2) are key transducers of G protein-coupled receptor (GPCR) signaling, orchestrating both shared and isoform-specific intracellular pathways. Phosphorylation of the receptor C-terminal tail by GPCR kinases encodes regulator...

Ligand Dissociation Pathways from Membrane Receptors Revealed by Weighted Ensemble Simulations.

The journal of physical chemistry. B
G-protein-coupled receptors (GPCRs) are pivotal in cellular signal transduction and serve as key drug targets. Among them, the β-adrenergic receptors (βAR and βAR) regulate cardiovascular function and are activated by endogenous catecholamines, norep...

On Free Energy Calculations in Drug Discovery.

Accounts of chemical research
ConspectusThis Account discusses recent progress and challenges in binding free energy computations, focusing on two classes of enhanced sampling techniques: alchemical transformations and path-based methods. Binding free energy is a crucial metric i...

Efficient Exploration of High-Dimensional Configuration Spaces for the Generation of Chemical Datasets.

Journal of chemical information and modeling
In this work, we introduce an automated methodology for the efficient and relatively inexpensive exploration of large high-dimensional chemical spaces, with particular focus on number-of-atoms-conserving processes, such as in mechanochemical reaction...

ParametrizANI: Fast and Accessible Dihedral Parametrization for Small Molecules.

Journal of chemical information and modeling
In molecular studies, the accurate parametrization of small molecules stands as an essential yet growing demand. Addressing this, we introduce ParametrizANI, a tool crafted explicitly for establishing detailed protocols for dihedral parametrization u...

Virtual screening of salty peptides from enzymatic and fermented products of wheat gluten and its molecular mechanism of interaction with TMC4 receptor.

Food chemistry
The health risks associated with excessive sodium intake have prompted an exploration of natural salt substitutes. This study was oriented to explore the salty peptides from enzymatic and fermented products of wheat gluten (WG) with different degrees...

More Sophisticated Is Not Always Better: A Comparison of Similarity Measures for Unsupervised Learning of Pathways in Biomolecular Simulations.

The journal of physical chemistry. B
Finding process pathways in molecular simulations such as the unbinding paths of small molecule ligands from their binding sites at protein targets in a set of trajectories via unsupervised learning approaches requires the definition of a suitable si...

Using Time Dependent Rate Analysis to Evaluate the Quality of Machine Learned Reaction Coordinates for Biasing and Computing Kinetics.

The journal of physical chemistry. B
Having an accurate reaction coordinate (RC) is essential for reliable kinetic characterization of molecular processes, but there are few quantitative metrics to evaluate RC quality. In this study, we consider the dimensionless γ metric from the Expon...

SpatPPI: a geometric deep learning model for predicting protein-protein interactions involving intrinsically disordered regions.

Genome biology
Intrinsically disordered proteins and regions (IDRs) lack stable 3D structures, posing challenges for interaction prediction. We present SpatPPI, a geometric deep learning model tailored for IDPPI prediction. SpatPPI leverages structural cues from fo...

AI-driven protein pocket detection through integrating deep Q-networks for structural analysis.

Journal of computer-aided molecular design
Protein pockets, or small cavities on the protein surface, are critical sites for enzymatic catalysis, molecular recognition, and drug binding. Accurately identifying these pockets is crucial for understanding protein function and designing therapeut...