Computational Analysis of Heat Capacity Effects in Protein-Ligand Binding.

ABSTRACT: Heat capacity effects in protein-ligand binding as measured by calorimetric experiments have recently attracted considerable attention, particularly in the field of enzyme inhibitor design. A significant negative heat capacity change upon ligand binding implies a marked temperature dependence of the binding enthalpy, which is of high relevance for attempts to optimize protein-ligand interactions. In this work, we address the question of how well such heat capacity changes can be predicted by computer simulations. We examine a series of human thrombin inhibitors that all bind with ΔC_p values of about -0.4 kcal/mol/K and calculate heat capacity changes from plain molecular dynamics simulations of the bound and free states of the enzyme and ligand. The results show that accu

SUBMITTER: Koenekoop L 

PROVIDER: S-EPMC11238534 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature