TY  - JOUR
T1  - Searching for Allostery in Plant‑Derived Chemicals Using Structural Dynamics, Pocket Plasticity, and Mechanism Prioritization
A1  - Emma Wilson
A1  - Frederik De Jong
A1  - Lara Peters
JF  - International Journal of Pharmaceutical And Phytopharmacological Research
JO  - Int J Pharm Phytopharmacol Res
SN  - 2250-1029
Y1  - 2025
VL  - 15
IS  - 2
DO  - 10.51847/lkRrl7Ta7l
SP  - 109
EP  - 118
N2  - Natural‑product discovery is still frequently organized around the assumption that biologically useful ligands should be sought against structurally evident pockets and ranked primarily by predicted binding compatibility. That logic is incomplete for allosteric discovery because regulatory sites can be state‑dependent, transient, structurally cryptic, or functionally meaningful only through their coupling to distant protein regions. This theory article develops a dynamics‑centered framework for searching plant‑derived chemical space against moving rather than singular protein structures. The analysis integrates conformational ensembles, pocket plasticity, cryptic‑site discovery, residue‑communication analysis, natural‑product three‑dimensional complexity, and mechanism‑oriented molecular prioritization. The central proposal is that candidate allosteric discovery should be treated as a conditional matching problem between ligand properties and dynamically available regulatory microenvironments. Pocket visibility, persistence, communication coupling, ligand complementarity, and predicted perturbational consequences should therefore be kept analytically distinct rather than compressed into a single docking score. Plant‑derived molecular complexity is treated as a potentially useful source of shape, stereochemical, and interaction diversity, not as evidence that natural products are intrinsically enriched for allosteric activity. The resulting theory further separates predicted pocket occupancy from functional allosteric control and requires prospective experimental falsification. Its applicability is limited by conformational sampling, force‑field error, uncertain pocket energetics, model dependence, target‑class differences, and the possibility that a dynamically detectable cavity is neither ligandable nor regulatory. The framework is proposed as a testable discovery logic, not a validated scoring system or implementation‑ready pipeline.
UR  - https://eijppr.com/article/searching-for-allostery-in-plantderived-chemicals-using-structural-dynamics-pocket-plasticity-and-rosjtvpuucg6kly
ER  -