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Full-Text Articles in Physical Sciences and Mathematics
In Silico Modeling Of Ph-Optimum Of Protein-Protein Binding, Rooplekha C. Mitra, Zhe Zhang, Emil Alexov
In Silico Modeling Of Ph-Optimum Of Protein-Protein Binding, Rooplekha C. Mitra, Zhe Zhang, Emil Alexov
Publications
Protein-protein association is a pH-dependent process and thus the binding affinity depends on the local pH. In vivo the association occurs in a particular cellular compartment, where the individual monomers are supposed to meet and form a complex. Since the monomers and the complex exist in the same micro environment, it is plausible that they coevolved toward its properties, in particular, toward the characteristic subcellular pH. Here we show that the pH at which the monomers are most stable (pH-optimum) or the pH at which stability is almost pH-independent (pH-flat) of monomers are correlated with the pH-optimum of maximal affinity …
Computational Analysis Of Missense Mutations Causing Snyder-Robinson Syndrome, Zhe Zhang, Shaolei Teng, Liangjiang Wang, Charles E. Schwartz, Emil Alexov
Computational Analysis Of Missense Mutations Causing Snyder-Robinson Syndrome, Zhe Zhang, Shaolei Teng, Liangjiang Wang, Charles E. Schwartz, Emil Alexov
Publications
The Snyder-Robinson syndrome is caused by missense mutations in the spermine sythase gene that encodes a protein (SMS) of 529 amino acids. Here we investigate, in silico, the molecular effect of three missense mutations, c.267G>A (p.G56S), c.496T>G (p.V132G), and c.550T>C (p.I150T) in SMS that were clinically identified to cause the disease. Single-point energy calculations, molecular dynamics simulations, and pKa calculations revealed the effects of these mutations on SMS's stability, flexibility, and interactions. It was predicted that the catalytic residue, Asp276, should be protonated prior binding the substrates. The pKa calculations indicated the p.I150T mutation causes pKa changes …
On The Ph-Optimum Of Activity And Stability Of Proteins, Kemper Tally, Emil Alexov
On The Ph-Optimum Of Activity And Stability Of Proteins, Kemper Tally, Emil Alexov
Publications
Biological macromolecules evolved to perform their function in specific cellular environment (subcellular compartments or tissues); therefore, they should be adapted to the biophysical characteristics of the corresponding environment, one of them being the characteristic pH. Many macromolecular properties are pH dependent, such as activity and stability. However, only activity is biologically important, while stability may not be crucial for the corresponding reaction. Here, we show that the pH-optimum of activity (the pH of maximal activity) is correlated with the pH-optimum of stability (the pH of maximal stability) on a set of 310 proteins with available experimental data. We speculate that …
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.