Mutations play fundamental roles in evolution by introducing diversity into genomes that either can be advantageous or disadvantageous to the organism by affecting protein stability and/or interfering interactions between partners. Their effect on molecular level is manifested as alterations of wild type properties of the corresponding macromolecules. While experimental investigations are preferred, they are too expensive and time consuming to be applied on a large number of cases. Thus, we propose a series of approaches to model the molecular effects of non-synonymous mutations: SAAMBE-3D: a structure-based approach to predict protein-protein binding affinity change upon mutations; SAAMBE-SEQ: a completely sequence-based method to predict protein-protein binding affinity change upon mutations; SAAFEC-SEQ: a sequence-based method to predict the change of the folding free energy caused by mutations; and SAMPDI-3D: a structure-based method to predict the change of the binding free energy caused by mutations in protein or DNA. These methods are available as web servers and as a stand-alone code. They are benchmarked against experimental data and shown to be accurate and fast to be applied to genome-scale studies. In summary, we present a series of new approaches for studying the impact of missense mutations in proteins or DNA. They were successfully applied and evaluated in different predictive tasks and were shown to outperform earlier methods. All of them provide friendly web servers and stand-alone codes at http://compbio.clemson.edu/.

Web servers and stand-alone codes for modeling effect of mutations on thermodynamic properties of macromolecules

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.