IN SILICO PREDICTION OF HOST-PATHOGEN PROTEIN INTERACTIONS IN MALARIA AND DOCKING ANALYSIS OF IDENTIFIED POTENTIAL TARGET WITH MODIFIED INHIBITORS

Abstract

Infectious diseases such as malaria have been a major concern in the field of healthcare. One of the most severe form of malaria is caused by Plasmodium falciparum which kills millions of people annually. The malarial infection is initiated by the protein interactions between pathogen and host proteins and severity of the disease is related to the extent to which the biological processes are shifted due to these interactions. The outcome of this disturbance also depends on the immune response of the host and how the pathogen interaction with the host, which is governed by the protein-protein interactions. Therefore, It is essential to analyze the protein-protein interactions among the host and pathogen proteins for understanding the process and characterizing specific molecular mechanisms involved in pathogen persistence and survival. In this study, we intend to generate a complete protein-protein interaction network of human host and pathogen Plasmodium falciparum by integrating experimental data and computationally predicted interactions using interolog method. The highly interacting protein which was found to have important role in infection was considered as a potential target for drug development against malaria. According to the analysis α-tubulin, a pathogen protein is found to be essential for infection and is identified as a potential drug target. Inhibitors were designed by modifying amiprophos methyl by adding functional group at benzene ring and adding piperdine ring on its side chain. With the results of docking and binding affinity analysis, two modified inhibitors were found which showed better docking scores of -10.5 and -10.43 and has better binding affinity of -83.80 and -98.16 with target. This inhibitor can be can be considered as a potential drug molecule and can be further tested in vivo for its property as an anti-malarial drug.