The appropriate selection of initial receptor structure has been the "cornerstone" or foundation of successful structure-based virtual screening (SBVS), and plagued the structure-based design with a significantly practical problem to determine the major physiological states or important transition states of receptors (e.g. proteins with multiple low-energy conformations and ligand-dependent conformational dynamics). It is well known that current SBVS methods lack capacity to
capture and characterize the intrinsic receptor flexibility with ideal cost-effectiveness. In recent years, cryoelectron microscopy (cryo-EM) has been routinely applied in the determination of biomolecular assemblies within physiological state. In
this work, we review the roles of cryo-EM and ensemble docking methods to present the intrinsically dynamic behavior of
biomacromolecules, as well as the ever-improving estimation of ligand binding affinities and receptor-ligand thermodynamics. Finally, we also provide an attitude for the further researches on the modeling receptor dynamics.
Keywords: Molecular recognition, Receptor dynamics, Cryo-EM, Flexible docking, Molecular simulation
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