Computational strategies for modeling receptor flexibility in studies of receptor-ligand interactions

摘要

All biomolecular binding processes involve molecular dynamics, even those apparently corresponding to the rigid lock-and-key model. However, while it is becoming increasingly common to treat the flexibility of small ligands explicitly in drug design studies, the flexibility of macromolecular receptors is often ignored. Here, the different types of receptor motions on ligand binding are described and their implications for drug design discussed. Methods to model and simulate receptor dynamics on ligand binding are outlined. Their current usage in the context of structure-based drug design is described.