Neural Network Corrections to Intermolecular Interaction Terms of a Molecular Force Field Capture Nuclear Quantum Effects in Calculations of Liquid Thermodynamic Properties.

We incorporate nuclear quantum effects (NQE) in condensed matter simulations by introducing short-range neural network (NN) corrections to the ab initio fitted molecular force field ARROW. Force field NN corrections are fitted to average interaction energies and forces of molecular dimers, which are simulated using the Path Integral Molecular Dynamics (PIMD) technique with restrained centroid positions. The NN-corrected force field allows reproduction of the NQE for computed liquid water and methane properties such as density, radial distribution function (RDF), heat of evaporation (HVAP), and solvation free energy.

AMPA Receptor Noncompetitive Inhibitors Occupy a Promiscuous Binding Site.

Noncompetitive inhibitors of AMPA receptors have attracted interest in recent years as antiepileptic drugs. However, their development is hindered by a lack of detailed understanding of the protein-inhibitor interaction mechanisms. Recently, structures of AMPA receptor complexes with the structurally dissimilar, noncompetitive, small-molecule inhibitors pyridone perampanel (PMP), GYKI 53655 (GYKI), and CP 465022 (CP) were resolved, revealing that all three share a common binding site.

A Hierarchical Approach to Predict Conformation-Dependent Histidine Protonation States in Stable and Flexible Proteins.

Solution acidity measured by pH is an important environmental factor that affects protein structure. It influences the protonation state of protein residues, which in turn may be coupled to protein conformational changes, unfolding, and ligand binding. It remains difficult to compute and measure the p K of individual residues, as well as to relate them to pH-dependent protein transitions.