Atomic-level binding interaction analysis of Mycobacterium tuberculosis membrane protein Rv1085c with Toll-Like receptor 2 to investigate its role in immune response.

Abstract

The sequencing of the entire Mycobacterium tuberculosis (Mtb) genome in 1998 opened the door to exciting discoveries about the cellular and molecular underpinnings of the pathogen's virulence and capability to persist within host cells. One of the potential contributing gene to this virulence and persistence is Rv1085c, which is a potential membrane protein in the Mtb H37Rv strain. Rv1085c has been annotated in databases such as MycoBrowser; however the structural and functional characteristics of Rv1085c have not been addressed in detail. In this study, we conducted an in silico structural and functional characterization of Rv1085c to further our understanding of its potential role in Mtb virulence. The 3D model of the Rv1085c protein was generated using the I-TASSER server and subjected to structural validation using a number of tools including PROCHECK, ProSA-web and Verify3D. Functional predictions provided evidence to suggest Rv1085c could be involved in processes related to virulence, detoxification pathway and host adaptation. Protein-protein docking studies were performed to examine potential host-pathogen interactions using ZDOCK and docking of Rv1085c against Toll-like receptor 2 (TLR2) (PDB ID: 5D3I), an important receptor that participates in innate immune recognition of Mtb. Molecular dynamics simulations (MDS) were also performed to analyse the stability and conformational dynamics of the Rv1085c-TLR2 complex. These results provide preliminary insights on structure and interaction with Rv1085c, suggesting its potential role in host immune modulation. This research offers insights for ulterior experimental verifications and may lead to a better identification of drug targets related to tuberculosis.