Prediction of structure of mycobacterial efflux pump protein Rv0194 and molecular dynamics simulation of the predicted structures

Abstract

Tuberculosis is a major cause of morbidity and mortality primarily in developing nations. The rising number of cases of multidrug resistance and extensive drug resistance are a critical concern for the management of the condition. Even though new antibiotics are being developed, eventually there are also strains that are resistant to them. The evolution of resistance in Mycobacterium tuberculosis is significantly influenced by drug efflux caused by efflux pumps. Rv0194 is an important efflux pump associated with resistance to multiple drugs like beta lactam antibiotics like ampicillin and also erythromycin and novobiocin. The introduction of efflux inhibitors for Rv0194 could shorten the course of current therapy and improve the efficacy of second-line medications. Building a trustworthy molecular model of this efflux pump is the goal of this study. We created 3 models using different modeling tools. These models were then subjected to a 20 ns molecular dynamics simulation in a lipid bilayer. We find that the model built by Swiss Model shows the best results in molecular modeling and validation and the structure is also stable throughout the 20 ns MD simulations. Consequently, this model is reliable and can be used for further studies.