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

利用计算机实验预测和控制核酸结合蛋白的碱基序列识别能力。

• 批准号: 14598001
• 负责人: SAITO Minoru
• 金额: $ 1.41万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14598001/
• 关键词: computer experiment; DNA binding protein; binding affinity; free energy calculation; MD simulation; molecular substitution; DNA; 塩基配列; 塩基置換; 塩基配列の認識; 蛋白質; 結合自由エネルギー

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.

这项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结合蛋白与DNA之间的结合亲和力，该方法是为了计算出野生型蛋白质和突变蛋白之间的展开自由能差而开发的。另一个目的是使用开发的方法阐明DNA结合蛋白碱序列识别的分子机制。为了完成目的，我可以将DNA碱基替换为其他碱基，以作为简单的情况，即胸腺素→尿嘧啶替代。我们计算了由于胸腺氨酸→尿嘧啶取代DNA-λ-压迫剂复合物引起的结合自由能的变化。计算出的值（1.5kcal/mol）与各自的实验值（1.8kcal/mol）非常吻合。我们阐明了λ压迫器如何在原子水平的细节上识别胸腺氨酸→尿嘧啶之间的微小差异。

项目成果

Saito M, Sarai A: "Free energy calculations for the relative binding affinity between DNA and λ-repressor"PROTEINS, 2003. (in press). (2003)

Saito M、Sarai A：“DNA 和 λ 阻遏物之间相对结合亲和力的自由能计算”蛋白质，2003 年。（出版中）。

斎藤稔: "化学フロンティア8、生体系のコンピュータ・シミュレーション"化学同人. 262 (2003)

Minoru Saito：“化学前沿 8，生物系统的计算机模拟” Kagaku Doujin 262 (2003)。

Minoru Saito, Kenji Sayano: "Acceleration of molecular dynamics simulations of proteins on the Earth Simulator by vectorization and parallelization."High Performance Computing Systems. 81-86 (2004)

Minoru Saito、Kenji Sayano：“通过矢量化和并行化加速地球模拟器上蛋白质的分子动力学模拟。”高性能计算系统。

Saito M, Sarai A: "FIee energy calculations for the relative binding affinity between DNA and λ-repressor"PROTEINS. 52. 129-136 (2003)

Saito M，Sarai A：“DNA 和 λ 阻遏物之间相对结合亲和力的 FIee 能量计算”蛋白质 52. 129-136 (2003)。

Minoru Saito, Akinori Sarai: "Free energy calculations for the relative binding affinity between DNA and λ-repressor."PROTEINS. vol.52. 129-136 (2003)

Minoru Saito，Akinori Sarai：“DNA 和 λ 阻遏物之间的相对结合亲和力的自由能计算”。蛋白质。第 52 卷。