The key role of the dynamics and flexibility of proteins in functional mechanisms: How computational methods can...

Despite its relevance, the well-known paradigm that connects sequence, structure and function still overlooks an important factor: the dynamics of the proteins involved in functional mechanisms. Experimental techniques such as nuclear magnetic resonance and, more recently, cryo-electron microscopy, provide some insight into the conformational diversity of a protein. However, technical difficulties limit their application to the proteome scale. Nevertheless, computational methods are now considered efficient in providing valuable information about the dynamical landscape of a given protein, thereby improving our understanding of its function. Among these methods, molecular dynamics simulations have become very popular and generate a large amount of data that can now be used by Artificial Intelligence approaches for prediction. This paper will describe and discuss the concepts and a few applications of these approaches.