Spatial analysis and quantification of the thermodynamic driving forces in protein-ligand binding: binding site variability.

ABSTRACT: The thermodynamic driving forces behind small molecule-protein binding are still not well-understood, including the variability of those forces associated with different types of ligands in different binding pockets. To better understand these phenomena we calculate spatially resolved thermodynamic contributions of the different molecular degrees of freedom for the binding of propane and methanol to multiple pockets on the proteins Factor Xa and p38 MAP kinase. Binding thermodynamics are computed using a statistical thermodynamics based end-point method applied on a canonical ensemble comprising the protein-ligand complexes and the corresponding free states in an explicit solvent environment. Energetic and entropic contributions of water and ligand degrees of freedom computed from the conf

SUBMITTER: Raman EP 

PROVIDER: S-EPMC4342289 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature