Conformational heterogeneity and protonation equilibria shape the photocycle branching in channelrhodopsin-2

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 140977 - 140977

Published: Feb. 1, 2025

Channelrhodopsin-2 is a photoactive membrane protein serving as an ion channel, gathering significant interest for its applications in optogenetics. Despite extensive investigation, several aspects of photocycle remain elusive and continue to be subjects ongoing debate. Of particular are the localization P480 intermediate within timing deprotonation glutamic acid E90, critical residue ChR2 functioning. In this study, we explore possibility early-P480 state, formed directly upon photoillumination dark-adapted where E90 deprotonated, hypothesized previous work [Kuhne et al. Proc. Natl. Acad. Sci. 116.19 (2019): 9380]. Employing extended molecular dynamics simulations, free energy calculations, computation infrared band associated with provide support model proposed by Kuhne Furthermore, our findings show that protonation state influenced diverse interconnected variables detail insights connect interaction pattern propensity. Our data demonstrate fact both protonated deprotonated possible depending on hydrogen bonding explaining mechanism at basis accumulation under continuous illumination.

Language: Английский

Accurate Prediction of CRISPR/Cas13a Guide Activity Using Feature Selection and Deep Learning

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

Published: March 17, 2025

CRISPR/Cas13a serves as a key tool for nucleic acid tests; therefore, accurate prediction of its activity is essential creating robust and sensitive diagnosis. In this study, we create dual-branch neural network model that achieves high accuracy classification performance across two independent data sets, outperforming previously published models relying solely on sequence features. The integrates direct encoding with descriptive features yields 99 out 1553, extracted through statistical analysis, which critically influence guide–target interactions Cas13a guide activity. By employing Shapley Additive Explanations Integrated Gradients feature importance show composition, mismatch type frequency, the protospacer flanking site region are primary These findings underscore using complementary inputs to deep learning-based provide valuable insights into mechanisms underlying interaction. All in all, study not only introduces reliable efficient but also offers foundation future rational design efforts.

Language: Английский

Investigation of pool boiling performance on a surface with copper nanowire arrays using molecular dynamics

International Journal of Heat and Fluid Flow, Journal Year: 2025, Volume and Issue: 114, P. 109818 - 109818

Published: March 19, 2025

Language: Английский