Abstract
Lupus Nephritis (LN) is an autoimmune disease affecting the kidneys, and conventional drug studies have limitations due to its imprecise and complex pathogenesis. Therefore, the aim of this study was to design a novel Lupus Nephritis-targeted drug with good clinical due potential, high potency and selectivity by computer-assisted approach.NIK belongs to the serine/threonine protein kinase, which is gaining attention as a drug target for Lupus Nephritis. we used bioinformatics, homology modelling and sequence comparison analysis, small molecule ab initio design, ADMET analysis, molecular docking, molecular dynamics simulation, and MM/PBSA analysis to design and explore the selectivity and efficiency of a novel Lupus Nephritis-targeting drug, ClImYnib, and a classical NIK inhibitor, NIK SMI1. We used bioinformatics techniques to determine the correlation between lupus nephritis and the NF-κB signaling pathway. De novo drugs design was used to create a NIK-targeted inhibitor, ClImYnib, with lower toxicity, after which we used molecular dynamics to simulate NIK SMI1 against ClImYnib, and the simulation results showed that ClImYnib had better selectivity and efficiency. Our research delves into the molecular mechanism of protein ligands, and we have designed and validated an excellent NIK inhibitor using multiple computational simulation methods. More importantly, it provides an idea of target designing small molecules.
Communicated by Ramaswamy H. Sarma
Authors’ contributions
Kaiyuan Z conceived, designed, and coordinated the study, validated the results, and reviewed the manuscript; Kaiyuan Z and Yingkai T designed and con-ducted the experiments, analyzed the data, and wrote initial manuscript; Kaiyuan Z, Yingkai T, Haiyue Y, Jingtao Y, Lu Tao reviewed the manuscript. Ping X oversaw all the work and provided funding. All authors read and approved the final manuscript.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Data availability statement
All raw data has been uploaded to https://github.com/kyang1027/ClImYnib. Any questions can be emailed to the first author.