Comparative Dynamics study of therapeutic drug target against multi-drug resistant Elizabethkingia anophelis

Abstract

Elizabethkingia anophelis is a gram-negative pathogenic bacterium, multiple drugs resistant, and becomes an opportunistic pathogen to cause various diseases such as neonatal meningitis and sepsis in individuals that are immune compromised. These diseases have been documented in areas classified as tropical or subtropical, including the Central African Republic, Singapore, and Hong Kong. E. anophelis bacteremia carries significant mortality and the fatality rate is alarmingly elevated, with a range of 24% to 60%. Having this dilemma, a computational study is proposed to discover the new medications to counter Elizabethkingia anopheles’ infections. A potential drug target acetyltransferase of Elizabethkingia anopheles is used in molecular docking that selected via a comprehensive literature review. Molecular docking procedure is performed against two distinct collections of compound libraries: Asinex and FDA. The GOLD software is employed to execute this procedure and the best 12 docked complexes are proceeded for further investigation and molecular dynamic simulation. To identity a novel potent drug to impede the function of the Acetyltransferase enzyme: various in-silico analyses are performed including ADMET assessment, molecular dynamics simulations, radial distribution function (RDF) analysis, evaluation of hydrogen bonding, calculation of binding energies, principal component analysis (PCA) and chemical characterization of top-complex. The outcomes from this proposed in-silico framework indicate that Acetyltransferase/Asinex-40 inclusion complex demonstrated notable inhibitory efficacy, suggesting its potential as promising drug candidates against the Acetyltransferase enzyme. However, it is crucial to conduct additional experimental validation through both in-vivo and in-vitro studies in order to confirm the therapeutic and prophylactic effects of these potential drugs.