Teng Shaolei, Srivastava Anand K, Schwartz Charles E, Alexov Emil, Wang Liangjiang
Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29634, USA.
Int J Comput Biol Drug Des. 2010;3(4):334-49. doi: 10.1504/IJCBDD.2010.038396. Epub 2011 Feb 4.
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.
本文描述了一种基于结构的方法，用于预测氨基酸取代对蛋白质功能的影响。使用同源建模方法预测结构。计算野生型和突变型结构之间的折叠和结合能差异，分别定量评估氨基酸取代对蛋白质稳定性和蛋白质-蛋白质相互作用的影响。我们证明，相互作用界面处的致病突变可能影响结合能并使蛋白质复合物不稳定，而非界面处的突变可能降低折叠能并使单体结构不稳定。结果表明，基于结构的分析可为理解疾病的分子机制提供有用信息。
