Mouse acetylcholinesterase unliganded and in complex with huperzine A: A comparison of molecular dynamics simulations

Sylvia Tara, T. P. Straatsma, J. Andrew McCammon

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34 Scopus citations

Abstract

A 1 ns molecular dynamics simulation of unliganded mouse acetylcholinesterase (AChE) is compared to a previous simulation of mouse AChE complexed with huperzine A (HupA). Several common features are observed. In both simulations, the active site gorge fluctuates in size during the 1 ns trajectory and is completely pinched off several times. Many of the residues in the gorge that formed hydrogen bonds with HupA in the simulation of the complex now form hydrogen bonds with other protein residues and water molecules in the gorge. The opening of a 'backdoor' entrance to the active site that was found in the simulation of the complex is also observed in the unliganded simulation. Differences between the two simulations include overall lower structural rms deviations for residues in the gorge in the unliganded simulation, a smaller diameter of the gorge in the absence of HupA, and the disappearance of a side channel that was frequently present in the liganded simulation. The differences between the two simulations can be attributed, in part, to the interaction of AChE with HupA.

Original languageEnglish
Pages (from-to)35-43
Number of pages9
JournalBiopolymers
Volume50
Issue number1
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • Acetylcholinesterase
  • Active site gorge
  • Backdoor
  • Gating
  • Huperzine A
  • Molecular dynamics simulations
  • Side channel

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