Quantitative Electronic Structure‐Activity Relations: The Influence of Basis Set Selection on Prediction Quality
Joaquín Lahsen, Helmut Schmidhammer, Mariana Spetea, Bernd Michael Rode · QSAR & Combinatorial Science · 2003
Abstract Quantitative electronic structure‐activity relations (QESAR) based on ab initio calculated atomic charge data have been investigated with respect to basis set influence on quality and predictability. A series of 11 nonpeptide δ‐opioid receptor ligands has been utilized to study the basis set effect, and to determine the active center of these compounds. The geometries were fully optimized using the semiempirical method AM1. Net atomic charges obtained from ab initio MO calculations were used as electronic predictors. Multivariate adaptive regression splines were applied to the data matrix for the construction of QESAR models, whose predictability was rated by PRESS. The best model yielded a PRESS value of 0.08 and it was obtained using the atomic charges derived from the basis set 6‐311G. This model contains the C(9), C(12), C(14), and O(19) atoms as predictors. The 3‐21G basis set supplies an almost equivalent model and can be seen as an economic alternative, therefore, for large compounds.