Multiscale Monte Carlo Sampling of Protein Sidechains: Application to Binding Pocket Flexibility.

ABSTRACT: We present a Monte Carlo sidechain sampling procedure and apply it to assessing the flexibility of protein binding pockets. We implemented a multiple "time step" Monte Carlo algorithm to optimize sidechain sampling with a surface generalized Born implicit solvent model. In this approach, certain forces (those due to long-range electrostatics and the implicit solvent model) are updated infrequently, in "outer steps", while short-range forces (covalent, local nonbonded interactions) are updated at every "inner step". Two multistep protocols were studied. The first protocol rigorously obeys detailed balance, and the second protocol introduces an approximation to the solvation term that increases the acceptance ratio. The first protocol gives a 10-fold improvement over a protocol that does not

SUBMITTER: Nilmeier J 

PROVIDER: S-EPMC2612633 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature