Journal: Biochemistry and Biophysics Reports

Article Title: Computational screening of walnut (Juglans regia) husk metabolites reveals Aesculin as a potential inhibitor of pectate lyase Pel3: Insights from molecular dynamics and τRAMD

doi: 10.1016/j.bbrep.2025.102171

Figure Lengend Snippet: RAMD-based evaluation of ligand dissociation dynamics for the Pel3–Aesculin complex. (a) Cumulative distribution function (CDF), tau (residence time) histogram, and (b) Kolmogorov–Smirnov (KS) test plot illustrates the rapid unbinding of Aesculin from the Pel3 active site, with a median dissociation time of ∼0.02 ns and a mean residence time of ∼0.015 ns. (C) The residence time histogram shows a near-normal distribution, confirmed by a Gaussian fit and KS test (p = 0.17), supporting the statistical reliability of the data. (d) The boxplot summarizes residence time dispersion across a single simulation replica, highlighting the presence of outliers that may reflect alternative dissociation pathways. (e) Distance plot showing the temporal evolution of the ligand's center-of-mass distance from the protein's active site, providing direct evidence of dissociation events and their timing during simulation Overall, the results reveal fast ligand dissociation, limited residence time, and suggest weak binding affinity between Aesculin and Pel3 under the simulated conditions.

Article Snippet: The final configurations from the three independent 100 ns MD simulations served as initial structures for τ-Random Acceleration Molecular Dynamics (τRAMD) simulations.

Techniques: Dispersion, Binding Assay