A fast method of large-scale serial semiempirical calculations of docking complexes

A brief survey of the state of the art in methods of calculations of protein—ligand interaction energies in docking complexes is presented. A new computational technique is proposed that allows one to fundamentally improve the performance of large-scale serial calculations of docking complexes using the AM1/PM3 semiempirical methods. The technique explicitly allows for a specific feature of docking problems, viz. , the need for calculating numerous ligand complexes with a specified protein whose noninteracting part remains “frozen” during computations. The interaction energies calculated using the new method differ only slightly from the results of complete AM1 calculations and the performance attained is high enough to solve practical drug design problems.