Predictive identification and design of potent inhibitors targeting resistance-inducing candidate genes from E. coli whole-genome sequences.

Introduction: This work utilizes predictive modeling in drug discovery to unravel potential candidate genes from Escherichia coli that are implicated in antimicrobial resistance; we subsequently target the gidB, MacB, and KatG genes with some compounds from plants with reported antibacterial potentials. Method: The resistance genes and plasmids were identified from 10 whole-genome sequence datasets of E. coli; forty two plant compounds were selected, and their 3D structures were retrieved and optimized for docking. The 3D crystal structures of KatG, MacB, and gidB were retrieved and prepared for molecular docking, molecular dynamics simulations, and ADMET profiling. Result: Hesperidin showed the least binding energy (kcal/mol) against KatG (-9.3), MacB (-10.7), and gidB (-6.7); additionally, good pharmacokinetic profiles and structure-dynamics integrity with their respective protein complexes were observed. Conclusion: Although these findings suggest hesperidin as a potential inhibitor against MacB, gidB, and KatG in E. coli, further validations through in vitro and in vivo experiments are needed. This research is expected to provide an alternative avenue for addressing existing antimicrobial resistances associated with E. coli's MacB, gidB, and KatG.

Troponin C gene mutations on cardiac muscle cell and skeletal Regulation: A comprehensive review.

BACKGROUND: The troponin complex plays a crucial role in regulating skeletal and cardiac contraction. Congenital myopathies can occur due to several mutations in genes that encode skeletal troponin. Moreover, there is limited information regarding the composition of skeletal troponin. This review specifically examines a comprehensive review of the TNNC gene mutations on cardiac and skeletal regulations. MAIN BODY: Troponin C (TNNC) has been linked to a newly discovered inherited muscle disorder. Genetic variations in genes that encode skeletal troponin can impair the function of sarcomeres. Various treatment approaches have been employed to mitigate the impact of variations, including the use of troponin activators, the injection of wild-type protein via AAV gene therapy, and myosin modification to enhance muscle contraction. The processes responsible for the pathophysiological implications of the variations in genes that encode skeletal troponin are not fully understood. CONCLUSION: This comprehensive review will contribute to the understanding of the relationship between human cardiomyopathy and TNNC mutations and will guide the development of therapy approaches.