Allosteric Modulator Fragment Library

Unlike highly conserved orthosteric sites, allosteric sites exhibit low conservation, high hydrophobicity, weak polarity, confined geometry, and dynamic cryptic properties. Rather than rigid keyhole-like cavities, they typically appear as flexible grooves, subunit interface clefts, or shallow depressions formed by protein conformational changes.

Based on the dynamic, hydrophobic, and elongated nature of allosteric pockets, MCE has carried out targeted fragment modification and screening under strict physicochemical criteria: MW 120–280 Da, HBD ≤ 2, HBA ≤ 3, PSA 30–80 Ų, rotatable bonds ≤ 2, cLogP 1–3.5. High 3D diversity was further ensured by PMI analysis, yielding fragments with excellent shape complementarity to allosteric pockets.

This library contains 1,800 structurally diverse, drug-like fragments, this library supports allosteric drug development and pocket optimization. It significantly improves screening hit rates and enables efficient, precise early-stage R&D of allosteric drugs.