On the Estimation of the Molecular Inaccessible Volume and the Molecular Accessible Surface of a Ligand in Protein Ligand Systems

In this work, a novel approach is proposed based on the accurate computation of a protein’s inaccessible volume as regards to a ligand, plus the corresponding surface area, where the ligand can be placed in order to “touch” the protein without any overlaps. The proposed approach can be thought as an extension of the widely used concept of the Solvent-Accessible Surface Area (SASA), evaluating the surface generated by the ligand while being rolled over all the atoms of the protein without penetrating them. Identification of the inaccessible volume of each candidate protein-ligand pair is also provided in the context of this study, along with the boundary surface where the ligand can be placed so as to be in “contact” with the protein, which is expected to significantly enhance the ability to investigate specific protein drug interactions.