NEW APPROACH TO THE RAPID SEMIEMPIRICAL CALCULATION OF MOLECULAR ELECTROSTATIC POTENTIALS BASED ON THE AM1 WAVE-FUNCTION - COMPARISON WITH AB-INITIO HF 6-31G ASTERISK RESULTS/

A new approach to the computation of molecular electrostatic potential s based on the AMI wave function is described. In contrast to the prev ailing philosophy, but consistent with the underlying NDDO approximati on, no deorthogonalization of the wave function is carried out. The in tegrals required for the computation of the electronic contributions t o the molecular electrostatic potential are evaluated in a manner simi lar to that of the AMI core-electron attraction integrals, while the n uclear contributions are computed using a new semiempirical function-Z (A)(s(A)s(A)s(p)s(p))[1 + exp[- omega(A)(R(Ai) - delta(A))]]-where the atomic parameters omega(A) and delta(A) are obtained by calibration a gainst the results of ab initio HF/6-31G calculations. Isopotential c ontour maps for guanine and cytosine obtained with the new method are qualitatively almost indistinguishable from their HF/6-31G counterpar ts, while quantitative comparisons for the minima for a wide range of molecules are reproduced with an rms error of 5.2 kcal mol-1. The loca tions of the ''lone-pair'' minima for a wide range of heterosubstitute d organic molecules generally fall within 0.02 angstrom of the corresp onding HF/6-31G minima while those in the pi-regions of unsaturated m olecules are generally within 0.2 angstrom. Because of the rapid integ ral evaluation, the fully semiempirical method described here is extre mely economical. For example, for the guanine-cytosine base pair it is >500 times faster than calculations in which the complete integral ma trix is computed analytically from the deorthogonalized AM1 wave funct ion. (C) 1993 by John Wiley & Sons, Inc.