Improved Molecular Docking of MAO-B Inhibitors with Glide

Abstract

Molecular docking is an essential structure-based technique that is frequently used for virtual screenings. In most cases, the precision of search algorithms of the modern docking programs is satisfactory. However, the scoring algorithms' accuracy is not sufficient to completely distinguish true positives from inactive solutions. Therefore, initial validation processes could elevate the docking enrichments. This paper proposes a validated molecular docking approach applying Glide’s HTVS mode to discover novel Monoamine Oxidase B (MAO-B) ligands. In addition, more precise docking modes (SP and XP) and the influence of free binding energy calculations (MM/GBSA) over the enrichment values were observed. The developed Glide’s docking protocol demonstrated good enrichment values, outperforming GOLD 5.3. Moreover, the XP docking mode displayed the most reliable results, while the utilization of SP and MM/GBSA simulations led to poor performances. Overall, we demonstrated that virtual screenings of large databases in 2V5Z utilizing HTVS mode followed by XP rescoring are suitable molecular docking protocols for acquiring novel MAO-B inhibitors.