Efficient automatic construction of atom-economical QM regions with point-charge variation analysis


The setup of QM/MM calculations is not trivial since many decisions have to be made by the simulation scientist to achieve reasonable and consistent results. The main challenge to be tackled is the construction of the QM region to make sure to take into account all important amino acid residues and exclude less important ones. In our previous work [J. Chem. Theory Comput. 65, 18, 2584–2596 (2022)], we introduced the point charge variation analysis (PCVA) as a simple and reliable tool to systematically construct QM regions based on the sensitivity of the reaction energy with respect to variations of the MM point charges. Here, we assess several simplified variants of this PCVA approach for the example of catechol O-methyltransferase and apply PCVA for another system, the triosephosphate isomerase. Furthermore, we extend its scope by applying it to a DNA system. Our results indicate that PCVA offers an efficient and versatile approach of the automatic construction of atom-economical QM regions, but also identify possible pitfalls and limitations.


Supplementary material

Supporting Information
Additional tables and figures.

Supplementary weblinks

Data Set
Data Set containing all necessary PDB files of the starting structures, the modified AMBER95 force field for the use with AMS, substrate and ion AMS fragment files, as well as the AMS input files for all geometry optimizations and single point calculations