Computational Studies on Acetylcholinesterase: Results from a FY 2002 DoD Challenge Project

Abstract

This report documents the initial phases (model development) of a DoD Challenge project investigating the interactions of organophosphorus compounds with acetylcholinesterase. This project entails characterization of the structural features, which lie al the heart of the interaction between novel organophosphorus compounds (or other more reversible inhibitors) and the enzyme acetylcholinesterase. Large biological systems present inherent difficulties to the modeling community. We are using quantum chemical and mixed quantum/classical techniques, QM/MM, to examine structural effects of reactions involving novel organophosphorus compound in the active site of the enzyme, as well as the role of surrounding residues. This investigation will provide highly accurate and reliable characterizations of the biochemical processes responsible for both activity and inhibition of novel organophosphorus compounds. It is expected that the results should prove relevant to toxicological endeavors within the medical and non-medical community alike.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2003
Accession Number
ADA414647

Entities

People

  • Gerald Lushington
  • J. B. Wright
  • Margaret Hurley
  • William R. White

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Acetylcholinesterases
  • Chemical Compounds
  • Communities
  • Enzymes
  • Inhibition
  • Inhibitors
  • Organophosphorus Compounds
  • Reversible
  • Systems Biology

Readers

  • Molecular and Cellular Biochemistry
  • Quantum Chemistry
  • Systems Analysis and Design

Technology Areas

  • Quantum Computing