Enhanced ligand sampling for relative protein-ligand binding free energy calculations.

ABSTRACT: Free energy calculations are used to study how strongly potential drug molecules interact with their target receptors. The accuracy of these calculations depends on the accuracy of the molecular dynamics (MD) force field as well as proper sampling of the major conformations of each molecule. However, proper sampling of ligand conformations can be difficult when there are large barriers separating the major ligand conformations. An example of this is for ligands with an asymmetrically substituted phenyl ring, where the presence of protein loops hinders the proper sampling of the different ring conformations. These ring conformations become more difficult to sample when the size of the functional groups attached to the ring increases. The Adaptive Integration Method (AIM) has been developed,

SUBMITTER: Kaus JW 

PROVIDER: S-EPMC4442669 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature