Prediction and control of base sequence recognition ability for nucleic acid binding proteins by using computer experiments.

本研究的目的是通过扩展我的方法（计算突变→MD模拟→自由能计算）来计算DNA结合蛋白和DNA之间的结合亲和力，该方法是为了计算野生型蛋白和突变蛋白之间的解折叠自由能差异而开发的。另一个目的是阐明DNA结合蛋白识别碱基序列的分子机制。为了完成这个目的，我可以在简单的情况下用一个DNA碱基替换其他碱基，即，胸腺嘧啶→尿嘧啶取代。我们计算了由于胸腺嘧啶→尿嘧啶取代DNA-λ-阻遏物复合物而引起的结合自由能变化。计算值（1.5kcal/mol）与相应的实验值（1.8kcal/mol）符合得很好。我们阐明了λ-阻遏物如何在原子水平上识别胸腺嘧啶→尿嘧啶之间的微小差异。

The purpose of this study was to calculate binding affinity between a DNA binding protein and a DNA by expanding my methodology(computational mutation→MD simulation→free energy calculation) which was developed to calculate unfolding free energy differences between a wild type protein and mutant proteins. Another purpose is to clarify the molecular mechanism of the base sequence recognition by DNA binding proteins using the developed method. To complete the purpose, I made it possible to substitute a DNA base to other bases for the simple case, i.e., thymine→uracil substitution. We calculated the binding free energy change due to the thymine→uracil substitution for the DNA-λ-repressor complex. The calculated value(1.5kcal/mol) was in good agreement with the respective experimental value(1.8kcal/mol). We clarified how the λ-repressor recognizes such small difference between thymine→uracil on the atomic level details.