title: A comparison of different electrostatic potentials on prediction accuracy in CoMFA and CoMSIA studies.
abstract: Computational chemistry is playing an increasingly important role in drug design and discovery, structural biology, and quantitative structure-activity relationship (QSAR) studies. For QSAR work, selecting an appropriate and accurate method to assign the electrostatic potentials of each atom in a molecule is a critical first step. So far several commonly used methods are available to assign charges. However, no systematic comparison of the effects of electrostatic potentials on QSAR quality has been made. In this study, twelve semi-empirical and empirical charge-assigning methods, AM1, AM1-BCC, CFF, Del-Re, Formal, Gasteiger, Gasteiger-Hückel, Hückel, MMFF, PRODRG, Pullman, and VC2003 charges, have been compared for their performances in CoMFA and CoMSIA modeling using several standard datasets. Some charge assignment models, such as Del-Re, PRODRG, and Pullman, are limited to specific atom and bond types, and, therefore, were excluded from this study. Among the remaining nine methods, the Gasteiger-Hückel charge, though commonly used, performed poorly in prediction accuracy. The AM1-BCC method was better than most charge-assigning methods based on prediction accuracy, though it was not successful in yielding overall higher cross-validation correlation coefficient (q(2)) values than others. The CFF charge model worked the best in prediction accuracy when q(2) was used as the evaluation criterion. The results presented should help the selection of electrostatic potential models in CoMFA and CoMSIA studies.
authors.affiliation: The Genomics Research Center, Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei 115, Taiwan.
authors.forename: Keng-Chang
authors.initials: KC
authors.lastname: Tsai
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Chen
authors.forename: Nai-Wan
authors.initials: NW
authors.lastname: Hsiao
authors.forename: Chao-Li
authors.initials: CL
authors.lastname: Wang
authors.forename: Chih-Lung
authors.initials: CL
authors.lastname: Lin
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Lee
authors.forename: Minyong
authors.initials: M
authors.lastname: Li
authors.forename: Binghe
authors.initials: B
authors.lastname: Wang
mesh_terms: D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D055672:Static Electricity