Elucidating the energetics of entropically driven protein-ligand association: calculations of absolute binding free energy and entropy.

ABSTRACT: The binding of proteins and ligands is generally associated with the loss of translational, rotational, and conformational entropy. In many cases, however, the net entropy change due to binding is positive. To develop a deeper understanding of the energetics of entropically driven protein-ligand binding, we calculated the absolute binding free energies and binding entropies for two HIV-1 protease inhibitors Nelfinavir and Amprenavir using the double-decoupling method with molecular dynamics simulations in explicit solvent. For both ligands, the calculated absolute binding free energies are in general agreement with experiments. The statistical error in the computed ΔG(bind) due to convergence problem is estimated to be ≥2 kcal/mol. The decomposition of free energies indicates that, althoug

SUBMITTER: Deng NJ 

PROVIDER: S-EPMC4127432 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature