Validation of Poisson-Boltzmann Electrostatic Potential Fields in 3D QSAR: A CoMFA Study on Multiple Datasets
G.E. Kellogg, S. Phatak, A. Nicholls and J.A. Grant, "Validation of Poisson-Boltzmann Electrostatic Potential Fields in 3D QSAR: A CoMFA Study on Multiple Datasets", QSAR & Combinatorial Science, 2004, 22 (9-10), pp 959-964
A CoMFA 3D QSAR (Quantitative Structure-Activity Relationships) study was performed on five diverse data sets that have been previously published or are otherwise generally available to assess the value of the ZAP electrostatic potential field (calculated from a solution of the Poisson-Boltzmann Equation) as compared to the Coulombic field as implemented in standard CoMFA. The ZAP field showed an average improvement of 0.114 in q2 (leave-one-out cross-validation) as compared to the Coulombic field, and the steric/ZAP combination field showed an improvement of 0.128 in q2 as compared to the Both (steric and electrostatic) field combination of CoMFA. However, the enhancement is not monolithic – some of the data sets in this study showed a much larger preference for the ZAP field than others. The ZAP field appears to be more physically realistic than the Coulombic field and should be of significant value in QSAR studies of some data sets.
