Cocaine esterase-cocaine binding process and the free energy profiles by molecular dynamics and potential of mean force simulations.

ABSTRACT: The combined molecular dynamics (MD) and potential of mean force (PMF) simulations have been performed to determine the free energy profiles for the binding process of (-)-cocaine interacting with wild-type cocaine esterase (CocE) and its mutants (T172R/G173Q and L119A/L169K/G173Q). According to the MD simulations, the general protein-(-)-cocaine binding mode is not affected by the mutations; e.g.. the benzoyl group of (-)-cocaine is always bound in a subsite composed of aromatic residues W151, W166, F261, and F408 and hydrophobic residue L407, while the carbonyl oxygen on the benzoyl group of (-)-cocaine is hydrogen-bonded with the oxyanion-hole residues Y44 and Y118. According to the PMF-calculated free energy profiles for the binding process, the binding free energies for (-)-cocaine wi

SUBMITTER: Huang X 

PROVIDER: S-EPMC3305836 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature