Method for the improved semiempirical description of intermolecular interactions of biomolecules and their fragments

Abstract

A new method was proposed for the improvement of the semiempirical (PM3, etc. levels of theory) description of intermolecular potential energy surfaces in biomolecules, primarily hydrophobic dispersion-type interactions. The intermolecular interaction energy calculated by the PM3 method is supplemented with the sum of atom-atom corrections represented in a physically meaningful functional form. The corresponding empirical parameters were selected by the least-squares procedure minimizing the root-mean-square deviation of the intermolecular interaction energies from the reference values calculated by the high-accuracy ab initio MP2 method with the quadruple zeta aug-cc-pVTZ basis set. The empirical parameters depend on the valence environment of atoms. The root-mean-square deviation for 74079 reference calculations of small-molecule dimers (with molecular fragments typical of docking complexes) is ∼1.6 kJ mol⁻¹, being about 2.5 times lower than that obtained from conventional PM3 calculations (∼4.0 kJ mol⁻¹). It is important to take into account weak intermolecular atom-atom pairwise interactions because there is a lot of such interacting pairs in biomolecules.