Strong Ligand-Protein Interactions Derived from Diffuse Ligand Interactions with Loose Binding Sites.

ABSTRACT: Many systems in biology rely on binding of ligands to target proteins in a single high-affinity conformation with a favorable ΔG. Alternatively, interactions of ligands with protein regions that allow diffuse binding, distributed over multiple sites and conformations, can exhibit favorable ΔG because of their higher entropy. Diffuse binding may be biologically important for multidrug transporters and carrier proteins. A fine-grained computational method for numerical integration of total binding ΔG arising from diffuse regional interaction of a ligand in multiple conformations using a Markov Chain Monte Carlo (MCMC) approach is presented. This method yields a metric that quantifies the influence on overall ligand affinity of ligand binding to multiple, distinct sites within a protein bindi

SUBMITTER: Marsh L 

PROVIDER: S-EPMC4434174 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature