| It is generally thought that proteins function by folding into stable three dimensional structures. However, it has recently become apparent that (parts of) proteins exist that are disordered within the cell. In particular, these disordered regions have been associated with complex life forms (e.g. humans) and with genes that are related to several diseases. Many of these proteins are thought to have a signaling function by binding to other proteins. It is unclear why these regions are disordered before binding; although several advantages of disordered regions have been proposed, as yet none have been found conclusive. Here we propose to simulate the binding process of natively disordered proteins to gain insights into the forces involved. In particular, we aim to investigate the relative importance of energetic and entropic contributions to the binding free energy. In order to carry out such simulations, we need to use a highly simplified model. A Monte Carlo simulation will be used to study the binding and folding process. Although the primary aim of this project is to gain understanding, we point out that, since disordered regions are associated with several diseases, greater understanding of disordered regions may have important implications for rational drug design. |
