| 蛋白质与极性配体复合物的绝对结合自由能计算 |
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| 引用本文： | 王存新,宋伟,陈慰祖.蛋白质与极性配体复合物的绝对结合自由能计算[J].生物化学与生物物理进展,2003,30(1):143-146. |
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| 作者姓名： | 王存新 宋伟 陈慰祖 |
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| 作者单位： | 北京工业大学生命科学与生物工程研究院,北京,100022 |
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| 基金项目： | 国家自然科学基金(29992590-2，30170230，10174005) 和北京市自然科学基金 (5032002)资助项目. |
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| 摘 要： | 介绍了用分子动力学模拟与热力学积分法相结合，模拟蛋白质与配体的绝对结合自由能的方法.通过分子转换法，使蛋白质分子（包括水分子）与配体小分子之间的相互作用逐渐减弱 （或增强）至完全消失（或完全出现）. 运用体约束方法，计算了配体与受体结合后平动、转动自由度的丧失即熵效应所引起的自由能变化.以胰蛋白酶双突变体（D189G/G226D）与极性配体苯甲脒为例，研究了蛋白质活性部位与极性配体的相互作用对结合自由能的影响，该复合物绝对结合自由能的模拟结果(－15.5 kJ/mol)与实验值(－10.5 kJ/mol)相近.
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| 关 键 词： | 分子转换法，热力学积分法，蛋白质-配体复合物，结合自由能 |
| 收稿时间： | 2002/8/12 0:00:00 |
| 修稿时间： | 2002年8月12日 |
The Absolute Free Energy Calculation of The Protein and Polar Ligand Complex |
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| WANG Cun-Xin,SONG Wei and CHEN Wei-Zu.The Absolute Free Energy Calculation of The Protein and Polar Ligand Complex[J].Progress In Biochemistry and Biophysics,2003,30(1):143-146. |
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| Authors: | WANG Cun-Xin SONG Wei and CHEN Wei-Zu |
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| Institution: | Institute of Life Science and Bioengineering, Beijing Polytechnic University, Beijing 100022, China;Institute of Life Science and Bioengineering, Beijing Polytechnic University, Beijing 100022, China;Institute of Life Science and Bioengineering, Beijing Polytechnic University, Beijing 100022, China |
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| Abstract: | Molecular dynamics simulation and thermodynamic integration method were used to calculate the absolute binding free energy of the protein- ligand complex. By the molecular transformation method, the interactions between protein (plus solvent) and its ligand are gradually decreased (or increased) into a non- interacting (or full interacting) state. A potential of a body restraint was used to calculate the free energy changes caused by the loss of translation and rotation freedom of the ligand molecule, that is called as the entropy effect. A mutant trypsin (D189G/G226D) and its polar ligand (benzamidine) were selected as a model to study the influence of the interactions between protein and polar ligand on the binding free energy. The calculation result of the absolute free energy for the model complex (-15 5 kJ/mol) is close to the experimental data ( -10 5 kJ/mol ). |
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| Keywords: | molecular transformation method thermodynamic integration method protein-ligand complex binding free energy |
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