In Silico Identification of Potential Dynamin-Related Protein 1 Antagonists: Implications for Diseases Involving Mitochondrial Dysfunction.

In this study, an integrated in silico strategy that includes homology modeling, pharmacophoric, docking analysis and molecular dynamics simulations was employed in designing the potential Drp1 inhibitors. A homology model of Drp1 was generated employing crystal structure of dynamin protein as a template. Pharmacophoric features were developed for the GTPase domain of dynamin-related protein 1 and were used to screen ZINC-database. The obtained hits were docked to the same domain. The binding mode analysis of these ligands showed all the essential binding interactions required in the inhibition of Drp1. Furthermore, explicit solvent simulations were carried out using the two most potential hits to validate the docking analysis and to study the overall stability of the binding site interactions. The present study not only provides a structural model of Drp1 for rational design of apoptotic inhibitors, but also identifies six potential compounds for further development. PMID: 23848310 [PubMed - as supplied by publisher]
Source: Combinatorial Chemistry and High Throughput Screening - Category: Chemistry Authors: Tags: Comb Chem High Throughput Screen Source Type: research