Protein–DNA interactions are essential for the regulations of many important cellular processes, such as transcription, replication, recombination and translation. Missense mutations occurring in DNA-binding protein have profound effect on protein-DNA interactions and are related with many diseases. In particular, the effect of mutations on binding affinity is one of the most important component of the overall disease effects. Hence, accurate prediction of missense mutations' effect on protein–DNA binding affinity is essential to understanding disease-causing mechanism and guiding protein engineering. A new methodology is developed to accurately predict the changes of the binding free energy caused by missense mutations on protein-DNA interactions. This new method utilizes modified molecular mechanics Poisson-Boltzmann Surface Area (MM/PBSA) approach along with an additional set of knowledge based terms delivered from investigation of the physico-chemical properties of protein-DNA complexes. An experimental dataset (combined ProNIT database with recent references) of experimentally determined binding free energy changes caused by 105 mutations in 13 proteins is used for training and benchmarking.

Predicting binding free energy change caused by missense mutations in protein-DNA interactions using modified MM/PBSA method

254th National Meeting (2017)

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