Combining simulations and experiments – a perspective on maximum entropy methods

Abstract

To elucidate the connection between the structure and function of intrinsically disordered proteins (IDPs) a description of their conformational ensembles is crucial. These are typically characterized by an extremely large number of similarly low energy conformations, which can hardly be captured by either experimental or computational means only. Rather, the combination of data from both simulation studies and experimental research offers a way towards a more complete understanding of these proteins. Over the last decade, a number of methods have been developed to integrate experimental data and simulations into one model to describe the conformational diversity. While many of these methods have been successfully applied, they often remain black-boxes for the scientist applying them. In this work, we review maximum entropy methods to optimize conformational ensembles of proteins. From a didactical perspective, we aim to present the mathematical concepts and the optimization processes in a common framework, to increase the understanding of these methods.