Calculation of the Absolute Free Energy of Binding and Related Entropies with the HSMD-TI Method: The FKBP12-L8 Complex.

ABSTRACT: The hypothetical scanning molecular dynamics (HSMD) method is used here for calculating the absolute free energy of binding, ΔA(0) of the complex of the protein FKBP12 with the ligand SB2 (also denoted L8) - a system that has been studied previously for comparing the performance of different methods. Our preliminary study suggests that considering long-range electrostatics is imperative even for a hydrophobic ligand such as L8. Therefore the system is modeled by the AMBER force field using Particle Mesh Ewald (PME). HSMD consists of three stages applied to both the ligand-solvent and ligand-protein systems. (1) A small set of system configurations (frames) is extracted from an MD trajectory. (2) The entropy of the ligand in each frame is calculated by a reconstruction procedure. (3) The co

SUBMITTER: General IJ 

PROVIDER: S-EPMC3274823 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature