补体蛋白C3c与抑制剂Compstatin的结合自由能计算  

Binding free energy calculation of complement protein C3c-inhibitor Compstatin interaction by MM/PBSA method

作　　者：杨威[1] 张峰[1] 马志[1] 郑俊峰[1] 

机构地区：[1]大连海洋大学农业部北方海水增养殖重点实验室,辽宁大连116023

出　　处：《大连海洋大学学报》2013年第2期154-159,共6页Journal of Dalian Ocean University

基　　金：国家自然科学基金资助项目(3047132)

摘　　要：采用分子动力学模拟取样,运用MM-PBSA方法计算了人类C3c-Compstatin复合物的结合自由能。通过能量分解方法探究了人类补体蛋白C3c上抑制剂结合域MG4～MG5(巨球蛋白区域)上的主要残基与配体Compstatin纤维蛋白之间的相互作用和识别。结果表明:C3c与补体抑制剂Compstatin的理论结合自由能(-8.06 kcal/mol)与试验值(-6.72 kcal/mol)吻合较好,分子内能总和(-177.24 kcal/mol)对补体抵制剂的结合贡献最大,其次为真空静电作用能(-108.74 kcal/mol)和范德华作用能(-68.51kcal/mol)。作为对结晶试验的补充,进行了C3c蛋白和小分子抑制剂之间结合的动态过程以及在两者结合的影响下蛋白形态变化的分子动力学模拟,结果发现C3c上的残基ARG459、ASP491、MET457和Compsta-tin上的残基TRP7、TRP4、HIS10为结合自由能作出了主要贡献。该结果对进一步研究C3补体抑制剂的机制提供了结构方面的信息。The binding free energy of human C3c-Compstatin complex was calculated by an MM/PBSA method, and the key residues interactions were also investigated between MCA-MG5 binding domain of C3c and Compstatin by using energy decomposition method. The results showed that the calculated binding free energy （- 8. 06 kcal/mol） was in high agreement with the binding affinity（-6.72 kcal/mol） by the experimental essays, the total energy in the molecule（ -177.24 kcaL/mol） showing the maximal contribution to binding complement inhibitor, followed by vaccum electrostatic interaction（-108.74 kcal/mol）and Van der Waals interaction（-68.51 kcal/mol）. The dynamic process of combination between C3c and the inhibitor together with the changes of the protein under the effect of combination was simulated as a complementary part in the crystal experiments. Our molecular dynamics stimulation proved the experiment with the structure information：Residue ARG459, ASP491, MET457 of C3c and TRP7 ,TRP4, HIS10 of Compstatin had major contribution to the binding free energy of the complex. The information above provides some insights into the based structural design of inhibitor of complement 3.

关 键 词：分子动力学 MM-PBSA GBSA方法 结合自由能 补体蛋白C3c 结合肽 

分 类 号：R331[医药卫生—人体生理学]