OPTIMIZING MOLECULAR DOCKING PROTOCOLS OF PYRROLE CONTAINING MAO-B INHIBITORS THROUGH CORRELATION COEFFICIENTS

Virtual screening is emerging as a highly applied technique for the search of hits since it significantly reduces the time required for the establishment of novel, effective compounds compared to high-throughput screening. Implementing correlation coefficients to determine if a molecular docking study is robust and reliable has been established as common practice in recent years. The aim of this work was to determine if a relevant pairwise correlation between the scoring functions (ChemPLP, GoldScore, Chemscore and ASP) of the docking software GOLD 5.2 and previously determined experimental data of pyrrole derivatives with MAO-B inhibitory activity could be achieved. In order to optimize the correlation coefficient, we calculated the Pearson’s and Spearman’s coefficients after each docking simulation with all four GOLD 5.2 scoring functions. Thereafter, we varied three changeable parameters – the size of the grid space, the side-chain flexibility and the presence of water molecules in the active site, to perceive if we could obtain better correlation values. The highest R2=0.79 was attained with the following docking settings: scoring function ChemPLP, grid size 12Å and no rotatable side chain residues. This work provides an applicable GOLD 5.2 docking protocol for a future virtual screening of novel MAO-B inhibitors with pyrrole moiety.