Structural Bioinformatics Laboratory, Department of Biochemistry and Pharmacy, Abo Akademi University, Tykistökatu 6A (BioCity), FI-20520 Turku, Finland.
J Comput Chem. 2010 Jun;31(8):1722-32. doi: 10.1002/jcc.21460.
The atom-centered partial charges-approximation is commonly used in current molecular modeling tools as a computationally inexpensive alternative to quantum mechanics for modeling electrostatics. Even today, the use of partial charges remains useful despite significant advances in improving the efficiency of ab initio methods. Here, we report on new parameters for the EEM and SFKEEM electronegativity equalization-based methods for rapidly determining partial charges that will accurately model the electrostatic potential of flexible molecules. The developed parameters cover most pharmaceutically relevant chemistries, and charges obtained using these parameters reproduce the B3LYP/cc-pVTZ reference electrostatic potential of a set of FDA-approved drug molecules at best to an average accuracy of 13 +/- 4 kJ mol(-1); thus, equipped with these parameters electronegativity equalization-based methods rival the current best non-quantum mechanical methods, such as AM1-BCC, in accuracy, yet incur a lower computational cost. Software implementations of EEM and SFKEEM, including the developed parameters, are included in the conformer-generation tool BALLOON, available free of charge at http://web.abo.fi/fak/mnf/bkf/research/johnson/software.php.
原子中心局域电荷近似法通常用于当前的分子建模工具中，作为一种计算成本较低的替代方法，用于模拟静电。即使在今天，尽管在提高从头计算方法的效率方面取得了重大进展，但局部电荷的使用仍然很有用。在这里，我们报告了 EEM 和 SFKEEM 基于电负性均衡方法的新参数，用于快速确定能够准确模拟柔性分子静电势能的局部电荷。开发的参数涵盖了大多数药物相关的化学物质，使用这些参数获得的电荷再现了一组 FDA 批准的药物分子的 B3LYP/cc-pVTZ 参考静电势能，最佳平均精度为 13 ± 4 kJ mol(-1)；因此，配备这些参数的电负性均衡方法在准确性上可与当前最好的非量子力学方法（如 AM1-BCC）相媲美，而计算成本却更低。EEM 和 SFKEEM 的软件实现，包括开发的参数，都包含在构象生成工具 BALLOON 中，可以在 http://web.abo.fi/fak/mnf/bkf/research/johnson/software.php 免费获得。
