Energetics of Ortho-7 (oxime drug) translocation through the active-site gorge of tabun conjugated acetylcholinesterase.

ABSTRACT: Oxime drugs translocate through the 20 Å active-site gorge of acetylcholinesterase in order to liberate the enzyme from organophosphorus compounds' (such as tabun) conjugation. Here we report bidirectional steered molecular dynamics simulations of oxime drug (Ortho-7) translocation through the gorge of tabun intoxicated enzyme, in which time dependent external forces accelerate the translocation event. The simulations reveal the participation of drug-enzyme hydrogen bonding, hydrophobic interactions and water bridges between them. Employing nonequilibrium theorems that recovers the free energy from irreversible work done, we reconstruct potential of mean force along the translocation pathway such that the desired quantity represents an unperturbed system. The potential locates the binding

SUBMITTER: Sinha V 

PROVIDER: S-EPMC3394793 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature