Open Access. Powered by Scholars. Published by Universities.®
Physical Sciences and Mathematics Commons™
Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 2 of 2
Full-Text Articles in Physical Sciences and Mathematics
Developing Hybrid Approaches To Predict Pka Values Of Ionizable Groups, Shawn Witham, Kemper Talley, Lin Wang, Zhe Zhang, Daquan Gao, Wei Yang, Emil Alexov
Developing Hybrid Approaches To Predict Pka Values Of Ionizable Groups, Shawn Witham, Kemper Talley, Lin Wang, Zhe Zhang, Daquan Gao, Wei Yang, Emil Alexov
Publications
Accurate predictions of pKa values of titratable groups require taking into account all relevant processes associated with the ionization/deionization. Frequently, however, the ionization does not involve significant structural changes and the dominating effects are purely electrostatic in origin allowing accurate predictions to be made based on the electrostatic energy difference between ionized and neutral forms alone using a static structure. On another hand, if the change of the charge state is accompanied by a structural reorganization of the target protein, then the relevant conformational changes have to be taken into account in the pKa calculations. Here we report a hybrid …
Structural Assessment Of The Effects Of Amino Acid Substitutions On Protein Stability And Protein-Protein Interaction, Shaolei Teng, Liangjiang Wang, Anand K. Srivastava, Charles E. Schwartz, Emil Alexov
Structural Assessment Of The Effects Of Amino Acid Substitutions On Protein Stability And Protein-Protein Interaction, Shaolei Teng, Liangjiang Wang, Anand K. Srivastava, Charles E. Schwartz, Emil Alexov
Publications
A structure-based approach is described for predicting the effects of amino acid substitutions on protein function. Structures were predicted using a homology modelling method. Folding and binding energy differences between wild-type and mutant structures were computed to quantitatively assess the effects of amino acid substitutions on protein stability and protein–protein interaction, respectively. We demonstrated that pathogenic mutations at the interaction interface could affect binding energy and destabilise protein complex, whereas mutations at the non-interface might reduce folding energy and destabilise monomer structure. The results suggest that the structure-based analysis can provide useful information for understanding the molecular mechanisms of diseases.