MOLECULAR SIMULATION AND STOCHASTIC DOMINANCE ANALYSIS OF LIGANDS IN DRUGS FOR TREATMENT OF TB/HIV USING THE WEIGHTED GAMMA-RAYLEIGH DISTRIBUTION

Abstract

The recent treatment for Tuberculosis involves a prolonged study of a combination of antibiotics with toxic side-effects and is associated with poor patient compliance. This has resulted to the multi-drug resistant (MDR) and extensively-drug resistant (XDR) strains of M. tuberculosis. The number of anti-TB drugs currently in the pipeline is insufficient to address this major health challenge. Therefore, there is an urgent need to discover and develop new and efficient drugs against TB. Studying the interaction and functioning of drug components is the first step in the discovery process and Molecular docking is one of the methods that have been used to study drug interaction and functioning. In this study, a molecular dynamics simulation study of ligands (Ethambutol, Isoniazid, Rifampicin, Streptomycin, Pyrazinamides) that are responsible for the effectiveness of Anti-TB/HIV therapy was carried out. Additionally, the Weighted Gamma-Rayleigh distribution (WGRD) is introduced in this research work, and used in testing the stochastic dominance of the binding affinity of the ligands to the Anti-TB/HIV drugs. Results showed that Rifampicin has higher binding affinity as it has (first order stochastically) dominated Streptomycin and Pyrazinamide. Isoniazid has (first order stochastically) dominated Ethambutol. Also, Isoniazid has great power in reducing toxicity of Anti-TB/HIV drug. The results from this study provide an avenue for good health policy and prospective planning, especially in Anti-TB/HIV drug development.