Structure and dynamics of sarin-inhibited acetylcholinesterase
| Authors | |
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| Year of publication | 2005 |
| Type | Article in Proceedings |
| Conference | Modeling Interactions in Biomolecules II |
| MU Faculty or unit | |
| Citation | |
| Field | Physical chemistry and theoretical chemistry |
| Keywords | computational chemistry;computer modeling;molecular dynamics;MD;acetycholinesterase;AChE;nerve agent;irreversible inhibition;sarin |
| Description | Serine protease acetylcholinesterase (AChE, EC 3.1.1.7) is one of the most crucial enzymes for nerve response and function. In cholinergic nervous system, AChE terminates transmission of neuronal impulses by catalysing the hydrolysis of neurotransmitter, acetylcholine. It is one of the most efficient enzymes ever known. Highly toxic organophosphorus compounds, such as sarin, soman or tabun (nerve agents), are able to inhibit AChE by phosphonylation of its active site serine. Severe nerve agent intoxication leads to muscle spasms, cessation of breathing and instantaneous death. Structure of nerve agent inhibited AChE is not exactly known although one crystallographic structure (1SOM) of soman inhibited AChE was published. Thus a model of sarin inhibited mouse AChE was constructed and molecular dynamics was calculated to further characterize its properties. The explicit solvent molecular dynamics simulation under NPT conditions was performed by the Amber program suite. Simulation temperature was 300K and TIP3P water model was used. The stability of secondary structures and interactions of residues in AChE active site during molecular dynamics were analysed. |
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