Journal of Molecular Modeling

, Volume 13, Issue 2, pp 381–392 | Cite as

Multipole electrostatic potential derived atomic charges in NDDO-methods with spd-basis sets

Original Paper


The recently introduced multipole approach for computing the molecular electrostatic potential (MEP) within the semiempirical neglect of diatomic differential overlap (NDDO) framework [Horn AHC, Lin Jr-H., Clark T (2005) Theor Chem Acc 114:159–168] has been used to obtain atomic charges of nearly ab initio quality by scaling the semiempirical MEP. The parameterization set comprised a total of 797 compounds and included not only the newly parameterized AM1* elements Al, Si, P, S, Cl, Ti, Zr, and Mo but also the standard AM1 elements H, C, N, O and F. For comparison, the ZDO-approximated MEP was also calculated analytically in the spd-basis. For the AM1*-optimized structures, single-point calculations at the B3LYP, HF and MP2 levels with the 6-31G(d) and LanL2DZP basis sets were performed to obtain the MEP. The regression analysis of all 12 combinations of semiempirical and ab initio MEP data yielded correlation coefficients of at least 0.99 in all cases. Scaling the analytical and multipole-derived semiempirical MEP by the regression coefficients yielded mean unsigned errors below 2.6 and 1.9 kcal mol−1, respectively. Subsequently, for 22 drug molecules from the World Drug Index, atomic charges were computed according to the RESP procedure using XX/6-31G(d) (XX=B3LYP, HF, MP2) and scaled AM1* multipole MEP; the correlation coefficients obtained are 0.83, 0.85 and 0.83, respectively. Figure: Schematic representation of the atomic charge generation: The molecular electrostatic potential (MEP) is calculated using the AM1* Hamiltonian; then the semiempirical MEP is scaled to DFT or ab initio level, and atomic charges are generated subsequently by the restraint electrostatic potential (RESP) fit method.


AM1* Semiempirical MO theory Atomic charges Molecular electrostatic potential Multipole 



The authors thank Dr. G. Wellein, G. Hager, and T. Zeiser from the Regionales Rechenzentrum Erlangen (RRZE) for providing a specially optimized AMBER compilation, and the Bioinformatics group (Prof. Dr. H. Sticht) for support with AMBER 8.

Supplementary material

894_2006_137_MOESM1_ESM.pdf (300 kb)
Supplemental data (PDF 306 kb)


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Computer Chemie CentrumFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

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