A new method for in-silico drug screening and similarity search using molecular dynamics maximum volume overlap...

We developed a new molecular dynamics simulation method for molecular overlapping (alignment) and ligand-based in-silico drug screening based on molecular similarity. The molecular system consists of the query compound and the other compound(s) selected from a compound library. The newly introduced intermolecular interaction between compounds is proportional to the molecular overlap instead of the van der Waals and Coulomb interactions between atoms of different molecules. This method was able to achieve both conformer generation of molecules and molecular overlapping (alignment) at the same time. After an energy minimization and following short-time MD simulation, the molecules in the system were overlapped with each other and the similarity between compounds was measured by the volume of the overlap. We applied this MD simulation method to ligand-based in-silico drug screening and found that it worked well for several targets.