An efficient and accurate molecular alignment and docking technique using ab initio quality scoring

Abstract

An accurate and efficient molecular alignment technique is presented based on first principle electronic structure calculations. This new scheme maximizes quantum similarity matrices in the relative orientation of the molecules and uses Fourier transform techniques for two purposes. First, building up the numerical representation of true ab initio electronic densities and their Coulomb potentials is accelerated by the previously described Fourier transform Coulomb method. Second, the Fourier convolution technique is applied for accelerating optimizations in the translational coordinates. In order to avoid any interpolation error, the necessary analytical formulas are derived for the transformation of the ab initio wavefunctions in rotational coordinates. The results of our first implementation for a small test set are analyzed in detail and compared with published results of the literature. A new way of refinement of existing shape based alignments is also proposed by using Fourier convolutions of ab initio or other approximate electron densities. This new alignment technique is generally applicable for overlap, Coulomb, kinetic energy, etc., quantum similarity measures and can be extended to a genuine docking solution with ab initio scoring.

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“…Prior to molecular docking, the geometries of the compounds were quantum-mechanically (QM)-optimized using GAMESS-US [ 37 ] software (B3LYP/6-31G*). The optimized structures of the ligands were used with partial atomic charges derived from QM results [ 38 , 39 , 40 , 41 ] according to the Mulliken scheme [ 42 ] without torsion or any other degree of freedom for the ligands, which were frozen for molecular docking.…”