ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
2 files

Titr-DMD – A Rapid Constant pH Molecular Dynamics Framework

preprint
submitted on 04.02.2021, 20:35 and posted on 08.02.2021, 06:27 by David Reilley, Anastassia N. Alexandrova, Jian Wang, Nikolay Dokholyan
The pH dependence of enzyme fold stability and catalytic activity is a fundamentally dynamic, structural property which is difficult to study. Computational methods, particularly constant pH molecular dynamics (CpHMD), are the best situated tools for this. However, these often struggle with affordable sampling of sufficiently long timescales, accuracy of pKa prediction, and verification of the structures they generate. We introduce Titr-DMD, an affordable CpHMD method with a protonation state sampler that can be systematically improved, to circumvent these issues. We benchmark the method on a set of proteins with experimentally attested pKa and on the pH triggered conformational change in a staphylococcal nuclease mutant, a rare experimental study of such behavior. Our results show Titr-DMD to be an effective method to study pH coupled protein dynamics.

History

Email Address of Submitting Author

dreilley@chem.ucla.edu

Institution

University of California, Los Angeles

Country

United States

ORCID For Submitting Author

0000-0002-6877-9706

Declaration of Conflict of Interest

None

Exports

ChemRxiv

Exports