Born-Oppenheimer Ab Initio QM/MM Molecular Dynamics Simulations of Enzyme Reactions

Y. Zhou, S. Wang, Y. Li, Yingkai Zhang

Research output: Contribution to journalArticle

Abstract

There are two key requirements for reliably simulating enzyme reactions: one is a reasonably accurate potential energy surface to describe the bond-forming/breaking process as well as to adequately model the heterogeneous enzyme environment; the other is to perform extensive sampling since an enzyme system consists of at least thousands of atoms and its energy landscape is very complex. One attractive approach to meet both daunting tasks is Born-Oppenheimer ab initio QM/MM molecular dynamics (aiQM/MM-MD) simulation with umbrella sampling. In this chapter, we describe our recently developed pseudobond Q-Chem-Amber interface, which employs a combined electrostatic-mechanical embedding scheme with periodic boundary condition and the particle mesh Ewald method for long-range electrostatics interactions. In our implementation, Q-Chem and the sander module of Amber are combined at the source code level without using system calls, and all necessary data communications between QM and MM calculations are achieved via computer memory. We demonstrate the applicability of this pseudobond Q-Chem-Amber interface by presenting two examples, one reaction in aqueous solution and one enzyme reaction. Finally, we describe our established aiQM/MM-MD enzyme simulation protocol, which has been successfully applied to study more than a dozen enzymes.

Original languageEnglish (US)
Pages (from-to)105-118
Number of pages14
JournalMethods in Enzymology
Volume577
DOIs
StatePublished - 2016

Fingerprint

Molecular Dynamics Simulation
Molecular dynamics
Amber
Computer simulation
Enzymes
Static Electricity
Sanders
Sampling
Potential energy surfaces
Coulomb interactions
Electrostatics
Boundary conditions
Data storage equipment
Atoms
Communication

Keywords

  • Enzyme reaction
  • Free energy
  • Molecular dynamics
  • QM/MM
  • Simulation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Born-Oppenheimer Ab Initio QM/MM Molecular Dynamics Simulations of Enzyme Reactions. / Zhou, Y.; Wang, S.; Li, Y.; Zhang, Yingkai.

In: Methods in Enzymology, Vol. 577, 2016, p. 105-118.

Research output: Contribution to journalArticle

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