Combining Evolutionary Conservation and Quantum Topological Analyses to Determine QM Subsystems for Biomolecular QM/MM Simulations

10 May 2021, Version 2
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

We present an approach that combines protein sequence/structure evolution and electron localization function (ELF) analyses. The combination of these two analysis allows the determination of whether a residue needs to be included in the QM subsystem, or can be represented by the MM environment. We have applied this approach on two systems previously investigated by QM/MM simulations, 4{oxalocrotonate tautomerase (4OT), and ten-eleven translocation-2 (TET2), that provide examples where fragments may or may not need to be included in the QM subsystem. Subsequently, we present the use of this approach to determine the appropriate QM subsystem to calculate the minimum energy path (MEP) for the reaction catalyzed by human DNA polymerase lambda? with a third cation in the active site.

Keywords

QM/MM
topological analysis
ELF
evolution

Supplementary materials

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lambda 3mg reac
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Supplementary Information QMMM evol ELF
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