Characterization of hydrogen bonding in a continuum solvent model
Characterization of hydrogen bonding in a continuum solvent model
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DOI：
10.1021/jp9938967
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发表时间：
2000-07-13
影响因子：
3.3
通讯作者：
Mehler, EL
中科院分区：
文献类型：
--
作者：
Hassan, SA;Guarnieri, F;Mehler, EL
提出了一种计算多肽和蛋白质分子力学模拟中氢键(H键)效应的简单方法，用于前文所述的连续介质溶剂模型的框架中。在这种方法中，溶剂化的大分子被视为一个由溶剂、本体蛋白质和质子受体介质组成的三组分介电系统。氢键(H键)相互作用是通过极性氢和质子受体的范德华球的相互渗透来确定的。氢键几何结构的特征是受主原子中电子孤子对的理想取向和质子给体键的方向性，如实验和从头计算中所观察到的，并根据受主原子的杂化状态进行分类。该算法在CHARMM中使用PAR22力场实现。通过引入极性氢在受主环境中的出生半径的概念，可以通过一个简单的拟合过程来引入氢键能量的稳定。这种氢键描述很容易在标准力场中实现，几乎不需要额外的计算时间。用这种氢键处理和连续介质溶剂模型对两个多肽进行了蒙特卡罗模拟。结果清楚地表明了用所提出的连续统模型显式处理氢键的必要性，以及它从初级序列预测与实验结果一致的多肽结构的可靠性。
A simple approach for calculating hydrogen bonding (H-bonding) effects in molecular mechanics simulations of peptides and proteins is presented for use in the framework of the continuum solvent model described in the previous paper. In this approach, the solvated macromolecule is treated as a three-component dielectric system consisting of the solvent, bulk protein, and proton acceptor media. The hydrogen bond (H-bond) interaction is identified from the interpenetration of the van der Waals spheres of the polar hydrogen and the proton acceptor. The H-bond geometry is characterized by the ideal orientation of the electron lone pairs in the acceptor atom and the directionality of the proton donor bond, as observed in experimental and ab initio studies, and classified according to the hybridization state of the acceptor atom. The algorithm was implemented into CHARMM using the PAR22 force field. By introducing the concept of a Born radius of a polar hydrogen immersed in an acceptor environment, the stabilization of H-bond energies can be introduced by means of a simple fitting procedure. This H-bonding description is easily implemented in standard force fields, with virtually no additional computing time requirements. Monte Carlo simulations were carried out on two peptides with this H-bonding treatment and the continuum solvent model. The results clearly demonstrate the need for an explicit treatment of H-bonding with the proposed continuum model, and its reliability to predict peptide structures from the primary sequence that are in agreement with experimental results.