Abstract

PREDICTION OF CHLORAMPHENICOL AS PROTEIN-PROTEIN INTERACTION (PPI) INTERFACE INHIBITOR OF BACTERIAL UNIVERSAL STRESS PROTEIN (USPC) AND DNA POLYMERASE III SUBUNIT DELTA COMPLEX BY INTERGRATED QSAR AND QM/MM BASED DOCKING APPROACH

Alok Jha*

ABSTRACT

The study of protein interactions is important not only from a theoretical perspective but also in terms of potential practical implications because it might enable new drugs to be developed that can specifically disrupt protein interactions. The ability of small molecules to confer changes into specific PPIs can be pursued for designing small molecules that bind with high affinity to relatively large and at protein-protein interfaces. However, there are other sites that contrary to hot spots have an explicit concave/convex geometry appealing for therapeutic intervention. In this study we report Chloramphenicol (CAS Id 56-75-7) as inhibitor compound for the protein-protein interaction (PPI) interface of bacterial Universal Stress Protein (UspC), which has a functional role in providing resistance to DNA damaging agents and DNA polymerase III subunit delta that suggests a model for interaction of Pol III with the sliding clamp and DNA based on QSAR assisted QM/MM approach. The complex pharmacokinetic process, toxicity of the drug, bioaccumulation, mutagenicity and several molecular and topology based descriptors and accurate modeling of the protein-protein complex with the ligand, site of interactions, type of interactions and the docking method are combined to predict the complex drug metabolism process. Moreover, the integration of in silico methods based on a combination of QSAR, docking and QM/MM calculations can bring us one step further to understand drug metabolism and predict drug and its interaction with PPI interface.

Keywords: Protein-Protein Interaction, PPI inhibitor, QSAR, QM/MM, Docking, Toxicity.