Mittal Ruchi R, Harris Lisa, McKinnon Ross A, Sorich Michael J
Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia.
J Chem Inf Model. 2009 Mar;49(3):704-9. doi: 10.1021/ci800390m.
The 3D-QSAR method comparative molecular field analysis (CoMFA) involves the estimation of atomic partial charges as part of the process of calculating molecular electrostatic fields. Using 30 data sets from the literature the effect of using different common partial charge calculation methods on the predictivity (cross-validated R2) of CoMFA was studied. The partial charge methods ranged from the popular Gasteiger and the newer MMFF94 electronegativity equalization methods, to the more complex and computationally expensive semiempirical charges AM1, MNDO, and PM3. The MMFF94 and semiempirical MNDO, AM1, and PM3 methods for computing charges were found to result in statistically significantly more predictive CoMFA models than the Gasteiger charges. Although there was a trend toward the semiempirical charges performing better than the MMFF94 charges, the difference was not statistically significant. Thus, semiempirical partial charge calculation methods are suggested for the most predictive CoMFA models, but the MMFF94 charge calculation method is a very good alternative if semiempirical methods are not available or faster calculation speed is important.
三维定量构效关系方法比较分子场分析（CoMFA）在计算分子静电场的过程中涉及原子部分电荷的估算。利用文献中的30个数据集，研究了使用不同常见部分电荷计算方法对CoMFA预测能力（交叉验证R2）的影响。部分电荷方法涵盖了常用的Gasteiger方法和较新的MMFF94电负性均衡方法，以及更复杂且计算成本更高的半经验电荷方法AM1、MNDO和PM3。研究发现，与Gasteiger电荷相比，MMFF94以及半经验的MNDO、AM1和PM3电荷计算方法能得到统计学上预测性显著更高的CoMFA模型。尽管存在半经验电荷比MMFF94电荷表现更好的趋势，但差异在统计学上并不显著。因此，对于预测性最强的CoMFA模型建议使用半经验部分电荷计算方法，但如果无法使用半经验方法或计算速度更为重要，MMFF94电荷计算方法也是一个很好的选择。
