Alexov Emil
Howard Hughes Medical Institute and Biochemistry Department, Columbia University, New York, New York 10032, USA.
Proteins. 2003 Jan 1;50(1):94-103. doi: 10.1002/prot.10265.
The effect of the protein side-chain fluctuations on the strength of electrostatic interactions was studied. The effect was modeled on 7 different crystal structures on the same enzyme as well as on 20 molecular dynamics snapshot structures. It was shown that the side-chain flexibility affects predominantly the magnitude of the strong pair-wise interactions, that is, the pair-wise interaction among ion pairs, and practically does not affect the interactions with the rest of the protein. This was used to suggest a correction function that should be applied to the original pair-wise electrostatic interaction to mimic the effects of the fluctuations. The procedure is applied on three ion pairs identified in lysozyme. It was shown that sampling different side-chain rotamers and modifying the strength of the pair-wise interaction energies makes calculated pK(a)s less sensitive to the fluctuations of the structure and improves the prediction accuracy.
研究了蛋白质侧链波动对静电相互作用强度的影响。该影响在同一种酶的7种不同晶体结构以及20个分子动力学快照结构上进行了建模。结果表明，侧链灵活性主要影响强成对相互作用的大小，即离子对之间的成对相互作用，而实际上并不影响与蛋白质其余部分的相互作用。据此提出了一个校正函数，应将其应用于原始的成对静电相互作用以模拟波动的影响。该程序应用于溶菌酶中鉴定出的三个离子对。结果表明，对不同的侧链旋转异构体进行采样并修改成对相互作用能的强度，可使计算出的pK(a)对结构波动的敏感性降低，并提高预测准确性。
