In Silico Analysis of Binding Interactions between GSK983 and Human DHODH through Docking and Molecular Dynamics

Broad-spectrum antiviral agents are very important tools for combating emerging diseases. These small molecules target host cell and may prevent viral resistance development. However, these agents are more often cytotoxic and lower potential as drug candidates. Therefore, important in discovering drug which are broad-spectrum antivirals as well as nontoxic. The broad-spectrum antiviral known as GSK983, tetrahydrocarbazole amide derivative is discovered to help revived interest in these drugs. The chemotherapeutic therapy techniques to conserve antiviral effects of GSK983 while removing cytotoxicity is ground-breaking. Thus, identifying features associated with effective binding of GSK983 with its receptor HsDHODH could help in discovering other small molecules that could be combined molecular dynamics simulation. This study is showed GSK983 could be using novel interactions such as pi-cation (with Arg136), amide-pi (with Ala55 carbonyl group and His56 amine group) and pi-sulphur (with Met43) to stabilize its binding with HsDHODH by using different pre-docking and docking protocols with molecular dynamics simulation. Moreover, two hydrogen donors, two hydrogens and two tail-end hydrophobic rings on GSK983 allowed flexibility in binding to HsDHODH and generated binding modes in a binding site different from HsDHODH inhibitors such as BRE and A26 bind to. Therefore, these features on both ligand and receptor had been used to identify a host of new novel drugs which could be used in the combination therapy.