Ligand-induced conformational changes are of immense importance for the biological activity of a protein. An in-depth understanding of salutary and deleterious effects of ligand-induced conformational alterations in single- and multi-chain proteins would lend a hand in human welfare. Unlike single-chain proteins, the function of multichain proteins depends upon the inherent properties of the subunit interfaces. The interfaces of temporary oligomeric proteins and the active sites of enzymes are of similar characteristics but the interfaces are more conservative than the active sites. Therefore, these interfaces may possibly be represented as drug targets by inhibition or induction of the oligomerization process. Thus without detailed structural understanding of ligand-induced conformational changes in a protein, structure-based rational drug designing is a great challenging task. So the purpose of this review is to clarify or enlighten the reader at the degree of internal motions related to protein backbone and side-chain flexibility which occur on binding of small molecule to a protein target. This can prove helpful to improve the conformational prediction for a protein-ligand complex. Besides a detailed description of protein-ligand interaction, this review also focuses on structure-activity relationships of protein which will surely help in the rational drug designing.