Quantum mechanical studies of residue-specific hydrophobic interactions in p53-MDM2 binding
Quantum mechanical studies of residue-specific hydrophobic interactions in p53-MDM2 binding
复制标题
p53-MDM2 结合中残基特异性疏水相互作用的量子力学研究
DOI：
10.1021/jp8015886
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发表时间：
2008-09-11
影响因子：
3.3
通讯作者：
Zhang, John Z. H.
中科院分区：
文献类型：
--
作者：
Ding, Yun;Mei, Ye;Zhang, John Z. H.
在MP2/cc-pVDZ和MP2/cc-PVTZ水平上进行了量子化学计算，研究了疏水p53-MDM2结合界面上残基特异性相互作用。基于纳秒分子动力学模拟的结构计算结果显示，p53的（19）Phe、（22）Leu和（23）Trp与MDM2的结合相互作用最强，其次是（26）Leu和（27）Pro。MDM2与p53具有显性结合相互作用的特定残基被明确鉴定为（51）Lys, (54)Leu, (62)Met, (67)Tyr, (12)Gln, (94)Lys, (96)His和（100）Tyr。p53-MDM2的结合相互作用以范德华相互作用为主，其次是静电相互作用。MP2计算结果与力场计算结果基本一致，而DFT/B3LYP计算由于缺乏色散能而无法给出某些残-残相互作用的吸引相互作用能。
Quantum chemistry calculations at the levels of MP2/cc-pVDZ and MP2/cc-PVTZ have been carried out to study residue-specific interactions at the hydrophobic p53-MDM2 binding interface. The result of the calculation, based on structures from nanosecond molecular dynamics simulation, revealed that (19)Phe, (22)Leu, and (23)Trp of p53 have the strongest binding interaction with MDM2 followed by (26)Leu and (27)Pro. The specific residues of MDM2 that have dominant binding interactions with p53 are specifically identified to be (51)Lys, (54)Leu, (62)Met, (67)Tyr, (12)Gln, (94)Lys, (96)His, and (100)Tyr. The p53-MDM2 binding interaction is dominated by van der Waals interaction and to a lesser degree by electrostatic interaction. The MP2 results are in generally good agreement with those from the force field calculation while the DFT/B3LYP calculation failed to give attractive interaction energies for certain residue-residue interactions due to the lack of dispersion energy.