Activity Regulation and Conformation Response of Janus Kinase 3 Mediated by Phosphorylation: Exploration from Correlation Network Analysis and Markov Model DOI

Jian‐Zhong Chen,

Jian Wang, Wanchun Yang

et al.

Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

The activity of the enzyme JAK3 is modulated by tyrosine phosphorylation, yet underlying molecular details remain not fully understood. In this study, we employed a GaMD trajectory-based Markov model and correlation network analysis (CNA) to investigate impact single phosphorylation (SP) at Y980 (pY980) double (DP) Y980/Y981 (pY980/pY981) on conformational dynamics bound inhibitors IZA MI1. indicated that both SP DP result in fewer states significantly influence P-loop, αC-helix, loop1-loop3, while maintaining hinge region's high rigidity. CNA findings revealed alters communication among different structural regions JAK3, providing rational explanation for how affects distant P-loop loop1-loop3. Moreover, changes mediated further affect interactions between hot spots (L828, V836, E903, Y904, L905, L956) JAK3. This work offers valuable theoretical insights into mechanisms regulate activity.

Language: Английский

Insights into phosphorylation-induced influences on conformations and inhibitor binding of CDK6 through GaMD trajectory-based deep learning DOI
Lu Zhao, Jian Wang, Wanchun Yang

et al.

Physical Chemistry Chemical Physics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

GaMD trajectory-based deep leaning identifies phosphorylation-mediated effects on the function of CDK6.

Language: Английский

Citations

1
Discovering the natural source-derived antihypertensive compounds aspiring current therapeutic targets by computer-based drug design DOI
Nail Beşli, Nilufer Ercin, Rabia Kalkan Cakmak

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2025, Volume and Issue: 759, P. 151685 - 151685

Published: March 23, 2025

Language: Английский

Citations

0
Molecular dynamic simulations to assess the structural variability of ClpV from Enterobacter cloacae DOI Creative Commons
Tehrim Motiwala,

Babalwa Nyide,

Thandeka Khoza

et al.

Frontiers in Bioinformatics, Journal Year: 2025, Volume and Issue: 5

Published: March 25, 2025

The Enterobacter cloacae complex (ECC) consists of six species ( E. , hormaechei kobei ludwigii nimipressuralis and asburiae ) that have emerged as nosocomial pathogens interest, with hormachei being the most frequently isolated ECC in human clinical specimens intensive care unit (ICU) patients. Many outbreaks been related to transmission through contaminated surgical equipment operative cleaning solutions. As this pathogen evades action antibiotics, it is important find alternative targets limit devastating effects these pathogens. ClpV a Clp ATPase which dissociates recycles contracted sheath bacterial type VI secretion system (T6SS), thereby regulating populations facilitating environmental colonization. Seventy-one strains were mined for proteins. All investigated contained ClpA, ClpB, ClpX while only 20% ClpK. more than one protein, proteins showed significant variations. Three from strain E3442 then determine structural difference between each protein. Homology modelling be structurally similar other, however physicochemical characteristics vary. Additionally, analysis molecular dynamic simulations highly not significantly different other. Further investigation silico vitro presence absence various ligands could performed whether all interact their surroundings same manner. This would allow why multiple homologs protein are expressed by

Language: Английский

Citations

0
Activity Regulation and Conformation Response of Janus Kinase 3 Mediated by Phosphorylation: Exploration from Correlation Network Analysis and Markov Model DOI

Jian‐Zhong Chen,

Jian Wang, Wanchun Yang

et al.

Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

The activity of the enzyme JAK3 is modulated by tyrosine phosphorylation, yet underlying molecular details remain not fully understood. In this study, we employed a GaMD trajectory-based Markov model and correlation network analysis (CNA) to investigate impact single phosphorylation (SP) at Y980 (pY980) double (DP) Y980/Y981 (pY980/pY981) on conformational dynamics bound inhibitors IZA MI1. indicated that both SP DP result in fewer states significantly influence P-loop, αC-helix, loop1-loop3, while maintaining hinge region's high rigidity. CNA findings revealed alters communication among different structural regions JAK3, providing rational explanation for how affects distant P-loop loop1-loop3. Moreover, changes mediated further affect interactions between hot spots (L828, V836, E903, Y904, L905, L956) JAK3. This work offers valuable theoretical insights into mechanisms regulate activity.

Language: Английский

Citations

0