中文摘要：

将分子动力学模拟和分子力学-泊松／波耳兹曼方法相结合，研究在HIV蛋白酶和抑制剂ABT-538的复合物中的不同质子化位置．结果表明：不同的质子化状态对蛋白酶的温度因子、蛋白酶和抑制剂的结合自由能及氢键都有很大影响．用分子力学-泊松／波耳兹曼方法计算显示：在B链中，25号天冬氨酸ODI氧原子被质子化的结合自由能最强，计算得到的温度因子和实验值比较吻合．另外，由氢键分析看出：在此质子化状态中，药物和蛋白酶、药物和w301水分子、W301水分子和蛋白酶形成的氢键在整个动力学模拟过程中最稳定．

英文摘要：

Molecular dynamics simulations combined with the molecular mechanics- Poisson/Boltzmann surface area （MM-PBSA） are used to study the different protonation states in HIV-1 protease and ABT- 538. The results obtained demonstrate that different protonation states have strong influence on the Bfactor of protease, the binding free energy between protease and inhibitor and the hydrogen bond. The computation using the MM-PBSA method shows that protonation at the OD1 of Asp25 in B chain has the strongest binding free energy and the B-factor calculated is in agreement with the experiment data, Otherwise, the hydrogen analysis shows the hydrogen bonds between the inhibitor and protease, inhibitor and the bridged - water （W301）, and W301 and protease are most stable in the MD.