Abstract
The binding of many proteins to their protein partners is tightly regulated via control of their relative intrinsic dynamics during the binding process, a phenomenon which can in turn be modulated. Therefore, investigating the intrinsic dynamics of proteins is necessary to understand function in a comprehensive way. By intrinsic dynamics herein, we principally refer to the vibrational signature of a protein molecule popularly obtained from normal modes or essential modes. For normal modes, one often considers that the molecule under investigation is a collection of springs in a solvent-free or implicit-solvent medium. In the context of a protein-binding partner, the analysis of vibration of the target protein is often complicated due to molecular interaction within the complex. Generally, it is assumed that the isolated bound conformation of the target protein captures the implicit effect of the binding partner on the intrinsic dynamics, therefore suggesting that any influence of the partner molecule is also already integrated. Such an assumption allows large-scale studies of the conservation of protein flexibility. However, in cases where a partner protein directly influences the vibration of the target via critical contacts at the protein-protein interface, the above assumption falls short of providing a detailed view. In this review article, we discuss the implications of considering the dynamics of a protein in a protein-protein complex, as modelled implicitly and explicitly with methods dependent on elastic network models. We further propose how such an explicit consideration can be applied to understand critical protein-protein contacts that can be targeted in future studies.