Theoretical and Computational Chemistry

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



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


Thumbnail image of QMMM_Evol_ELF.pdf

Supplementary material

Thumbnail image of lambda_3mg_reac.mp4
lambda 3mg reac
Thumbnail image of Supplementary_Information_QMMM_evol_ELF.pdf
Supplementary Information QMMM evol ELF