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Title: Large-Scale First-Principles Molecular Dynamics Simulations with Electrostatic Embedding: Application to Acetylcholinesterase Catalysis

Journal Article · · Journal of Chemical Theory and Computation
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  1. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
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Enzymes are complicated solvated systems that typically require many atoms to simulate their function with any degree of accuracy. We have recently developed numerical techniques for large scale First-Principles molecular dynamics simulations and applied them to study the enzymatic reaction catalyzed by acetylcholinesterase. We carried out Density functional theory calculations for a quantum mechanical (QM) sub- system consisting of 612 atoms with an O(N) complexity finite-difference approach. The QM sub-system is embedded inside an external potential field representing the electrostatic effect due to the environment. We obtained finite temperature sampling by First-Principles molecular dynamics for the acylation reaction of acetylcholine catalyzed by acetylcholinesterase. Our calculations shows two energies barriers along the reaction coordinate for the enzyme catalyzed acylation of acetylcholine. In conclusion, the second barrier (8.5 kcal/mole) is rate-limiting for the acylation reaction and in good agreement with experiment.

Research Organization:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC52-07NA27344
OSTI ID:
1241999
Report Number(s):
LLNL-JRNL-673806
Journal Information:
Journal of Chemical Theory and Computation, Vol. 11, Issue 12; ISSN 1549-9618
Publisher:
American Chemical SocietyCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 6 works
Citation information provided by
Web of Science

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Cited By (3)

Applications of large-scale density functional theory in biology journal August 2016
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