Theoretical and Computational Chemistry

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

G. Andres Cisneros University of North Texas

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.

Version notes

version 1.0

Content

Thumbnail image of QMMM_Evol_ELF.pdf
download asset QMMM_Evol_ELF.pdf 25 MB [opens in a new tab]

Supplementary material

Thumbnail image of lambda_3mg_reac.mp4
download asset lambda_3mg_reac.mp4 0.57 MB [opens in a new tab]
lambda 3mg reac
Thumbnail image of Supplementary_Information_QMMM_evol_ELF.pdf
download asset Supplementary_Information_QMMM_evol_ELF.pdf 18 MB [opens in a new tab]
Supplementary Information QMMM evol ELF