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分子动力学 |
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MM-PBSA |
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结合自由能 |
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HIV-1 蛋白酶 |
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质子化态 |
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时术华 |
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扈国栋 |
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陈建中 |
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张少龙 |
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张庆刚 |
| PubMed | |
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Article by Shi, S. H. |
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Article by Hu, G. D. |
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Article by Chen, J. Z. |
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Article by Zhang, S. L. |
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Article by Zhang, Q. G. |
2. 山东师范大学 物理与电子科学学院
3. 山东师范大学物理与电子科学学院
I 型人体免疫缺陷病毒(HIV-1)蛋白酶中Asp25/Asp25'的质子化对于理论研究HIV-1 蛋白酶和抑制剂的作用机制
以及氨基酸变异对抗药性的影响有重要意义. 分别对Protease-Indinavir (PR-IDV)复合物的六种可能的质子化态进行了
5 ns 的分子动力学模拟, 分析了不同状态对动力学特征和结构的影响, 用molecular mechanics/Possion-Boltzman surface
area (MM-PBSA)方法计算了PR 和IDV 在各种状态下的结合自由能. 计算结果说明A 链Asp25 的OD2 的质子化是最
为可能的状态. 对PR-IDV 复合物中起到媒介作用的水分子与PR-IDV 复合物形成的氢键进行了分析, 分析结果说明不
同的质子化态对水分子在PR-IDV 复合物中所起的媒介作用没有影响, 这一结果与我们先前对PR-BEA369 复合物的研
究不同. 我们的研究结果为更高效的PR 抑制剂的设计以及PR 氨基酸变异对药物抗药性的研究提供了理论上的指导.
The protonation state of Asp25/Asp25' in Protease-Indinavir (PR-IDV) complex is important for
HIV-1 protease to study the binding mechanism and the drug resistance induced by the mutation in theory.
The 5 ns molecular dynamic simulations have been performed for six possible protonation states, the influences
on dynamics behavior and structure caused by different protonation states analyzed, and relative binding
free energies calculated using the molecular mechanics/Possion-Boltzman surface area (MM-PBSA)
method. The results show that the protonation state of OD2 from Asp25 in chain A is the most possible. The
hydrogen bonds between the water molecule that plays a medium role and the PR-IDV complex were also
analyzed, and the results show that the different states have not obvious influences on the medium role,
which is different from our previous result on PR-BEA369 complex. It was expected that this study could
provide a significative help for the high affinity inhibitor design and the mutation induced drug resistance
research.
国家自然科学基金（Nos. 10474060;10504017）;山东省自然科学基金（No. Q2006A06）资助项目
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