N Sukumar - Exploring Potent Ligand for Proteins: Insights from Knowledge-based Scoring Functions and Molecular Interaction Energies

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  Publication Details (including relevant citation   information):



  Suman Kumar   Mandal,Pinaki Saha, Parthapratim   Munshi, N. Sukumar,


  Struct.   Chem.28(5),   1537-1552 (2017).  DOI:   10.1007/s11224-017-1007-y



  Two different scoring functions, Hirshfeld fingerprint-based   scoring (HFBS) and molecular operating environment (MOE), and the   kernel energy method (KEM) along with counterpoise (CP)-corrected   approach were used to estimate the binding energies of   protein–ligand complexes and tested against a series of   inhibitors of human aldose reductase enzyme. The new scoring   function, HFBS, is based on Hirshfeld fingerprints, which are 2D   histogram plots of the distances from the molecular Hirshfeld   surface to the nearest atomic nuclei inside versus outside the   surface and are highly sensitive to the immediate environment of   the molecule. The Hirshfeld surface plotted over the ligand   molecule helped to visualize the contacts with the active site   residues and solvents, which were then taken into account for   interaction energy calculations. Application of KEM-assisted   CP-corrected approach facilitated an efficient way of calculating   interaction energies in protein complex systems. Interaction   energies calculated using MP2/6-31G(d) level of theory allowed us   to rank the ligands by potency. We find that both the KEMassisted   CP-corrected interaction energies and the scoring functions used   here predict comparable rankings for the strength of binding of   the series of ligands as docked to the active site of the   protein, which are also in good agreement with the experimental   binding affinities in this case.

  Address (URL): doi.org/10.1007/s11224-017-1007-y