title: Structural assessment of the effects of amino acid substitutions on protein stability and protein protein interaction.
abstract: 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.
authors.affiliation: Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29634, USA. steng@clemson.edu
authors.forename: Shaolei
authors.initials: S
authors.lastname: Teng
authors.forename: Anand K
authors.initials: AK
authors.lastname: Srivastava
authors.forename: Charles E
authors.initials: CE
authors.lastname: Schwartz
authors.forename: Emil
authors.initials: E
authors.lastname: Alexov
authors.forename: Liangjiang
authors.initials: L
authors.lastname: Wang
mesh_terms: D019943:Amino Acid Substitution; D019295:Computational Biology / Q000379:methods; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D017510:Protein Folding; D055550:Protein Stability