Investigation of salicylidene acylhydrazides derivatives: Molecular Docking, ADMET, and Molecular Dynamic Simulations were used in conjunction towards the design of new Yersinia pseudotuberculosis inhibitors

Abstract

LysR-type transcription factor RovM is an important target of Yersinia pseudotuberculosis drug discovery and the discovery of antibacterial is considered one of the greatest medical achievements of all time. In this research work, a combination of three docking tools with different algorithms was applied in Salicylidene acylhydrazides derivatives intended toward gram-negative bacterium Yersinia pseudotuberculosis to evaluate their binding interactions. The analysis of the molecular docking results obtained from the 3-docking software system succeeded in screening twelve fascinating compounds with higher restrictive concentrations having a decent affinity to LysR-type transcription factor RovM macromolecule. Then the Lipinski's and Veber's rule properties were calculated to spot the drug-likeness properties of the investigated candidate compounds. To anticipate the toxicity of the predicted candidate chemicals, in-silico toxicity tests were conducted. Furthermore, golden triangle and drug scores were performed, the investigated compounds which fall within the golden triangle indicate that these compounds would not have clearance problems. 5 of the 12 hits drugs pass the golden triangle screening step. These selected drugs undergo a drug score test which only compound 17 passed. To validate the stability, 1 ns molecular dynamic simulations were done on the highest-ranking drug score compound 17 / 3onm complexes. These findings point to interesting avenues for the development of new compounds that are more effective against Yersinia pseudotuberculosis.

Interactions and mechanisms of phenolic compounds with human immunodeficiency virus-1 Tat protein

“…This unfavorable interaction means that the potential energy of the system is decreased or less stable because of these interactions, or simply, two (or more) atoms do not like to be where they are. However, unfavorable interaction in molecular docking does not necessarily mean that the compound is not a good inhibitor because of many reasons such as protein flexibility is not taken into account in a commonly used docking protocol, the right binding mode of inhibitor might not be returned by the docking program or not top-scored by the used scoring function, other effects poorly accounted for in docking might play a crucial role in activity (solvent, entropy, and target interaction partners), and compound might have an unexpected mode of action or a different binding site [30]. Representation of binding interactions of the ligand-protein complexes with the highest negative binding affinity was selected based on the RMSD result of the ligand conformation.…”