物理化学学报 >> 2019, Vol. 35 >> Issue (1): 58-68.doi: 10.3866/PKU.WHXB201712141

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基于电负性均衡理论快速计算多肽分子中原子电荷的新方法

欧阳永中1,*(),花书贵2,邓金连1   

  1. 1 佛山科学技术学院 环境与化学工程学院,广东 佛山 528000
    2 江苏第二师范学院生命科学与化学化工学院,江苏省生物功能分子重点建设实验室,南京 210013
  • 收稿日期:2017-11-13 发布日期:2018-06-13
  • 通讯作者: 欧阳永中 E-mail:ouyang7492@163.com
  • 基金资助:
    国家自然科学基金(21405013);江苏省自然科学基金(BK20130748)

Rapid Assessment of Atoms-in-Molecules Charges for Polypeptides by the Electronegativity Equalization Method

Yongzhong OUYANG1,*(),Shugui HUA2,Jinlian DENG1   

  1. 1 School of Environmental and Chemical Engineering, Foshan University, Foshan 528000, Guangdong Province, P. R. China
    2 College of Life Science and Chemistry, Jiangsu Key Laboratory of Biological Functional Molecules, Jiangsu Second Normal University, Nanjing 210013, P. R. China
  • Received:2017-11-13 Published:2018-06-13
  • Contact: Yongzhong OUYANG E-mail:ouyang7492@163.com
  • Supported by:
    the National Natural Science of Foundation of China(21405013);Natural Science Foundation in Jiangsu Province of China(BK20130748)

摘要:

原子电荷在深入理解和模拟蛋白质的化学行为中发挥了重要的作用。通过校正电负性均衡方法(EEM)可快速计算大分子中原子电荷的分布情况。为进一步提高电负性均衡方法的准确性,本文根据Bader提出的分子区域片段中原子电荷高度转移理论,提出了一种校正电负性均衡理论的新方法,专门用于快速、准确计算生物大分子多肽或蛋白质中分子中原子电荷(AIM)。在EEM参数优化过程中,本方法不仅包括了不同原子间的连接性和价键的杂化属性,还考虑了分子片段或基团的区域化学环境因素对校正的影响。本研究对变量优化方法进行了深入讨论,微分进化算法被证明对目标函数有较好地表现。本方法计算的AIM电荷,与密度泛函理论的计算结果进行了比较。结果表明,与原来的EEM模型相比较,本方法计算的AIM电荷的精确度得到了大幅提高,为具有重复分子片段或基团的生物大分子体系(如多肽或蛋白质等)的原子电荷的快速计算提供了一种更为准确的方法,同时也为EEM的校正提供了一种新的思路。

关键词: 原子电荷, 电负性均衡方法, 分子中的原子电荷, 分子片段转移, 化学环境

Abstract:

Atomic charges play a crucial role in the understanding and modeling of the chemical behavior of proteins. Fast assessment of atomic charge distributions in larger molecules can be performed by implementing the electronegativity equalization method (EEM). To further improve the accuracy of the EEM approach, a novel and efficient method based on Bader's concept of high degree fragment transferability of atomic charges has been proposed for the parameterization of atoms-in-molecules (AIM) charges of polypeptides or proteins. The EEM parameterization method considers both the factors of connectivity and hybridized states, and the effect of the local chemical environment in fragments or groups. The types of atoms were defined on the basis of the local chemical environments of the fragments or functional groups of these atoms. The fragment transferability feature of QTAIM indicates that the atomic properties for the contributing atoms can be reproduced if the chemical environment is comparable. The constituent fragments or functional groups of macromolecules such as polypeptides and proteins can be utilized as building blocks for the additive generation of their electronic densities. The main peptide group (NH―HαCα―C=O) of the polypeptide in the backbone was used as a building block to model the EEM parameters for reproducing the atomic charges in the polypeptides. A training set of 20 terminally blocked amino acids (Ac-X-NHMe, X = any neutral residue), which recreated the immediate local environment of the main chain fragments or functional groups of the polypeptides, were chosen for the calibration of AIM charges using the differential evolution (DE) algorithm. The effects of the optimized methods on the results were discussed and it was found that the DE algorithm showed a better performance for the objective function. The quality of the AIM charges obtained from the EEM method presented in this study was evaluated by comparison with those obtained from B3LYP/6-31G+(d, p) calculations for the two test tetrapeptides not contained in the training set. It was found that a remarkable improvement was achieved using the EEM model developed in this study as compared to the previous studies. The introduction of Bader's high fragment charge transfer model into the EEM provided a new scheme for its calibration and parameterization for larger systems such as polypeptides or polynucleotides, which possess highly repetitive segments. Among all types of atomic charges, only the AIM charges showed a significant meaning in experiments and could be obtained by X-ray diffraction experiments. Rapidly reproducing the accurate AIM charge for large systems seems to be more meaningful, especially for the prediction of protein-protein, protein-DNA, and drug-receptor recognition and interactions.

Key words: Atomic charges, Electronegativity equalization method, AIM charges, Fragment transferability, Chemical environments

MSC2000: 

  • O641