IDPs couple folding and docking to their partner proteins. In the free-energy landscape of an IDP single chain, the folded structure is thermodynamically unstable. However, in the presence of a partner protein, an IDP folds to a tertiary structure, which is lowest in free energy. Our group performs computer simulations to investigate the free-energy landscape of this complicated coupled folding and docking process.

Initially, we perform conformational sampling of the system, which was expressed with an all-atom model in explicit water, to obtain an accurate free-energy landscape. We then use a coarse-grained model to obtain the coarse-grained free-energy landscape. In addition, we develop intermediately grained models to connect the free-energy landscapes from the coarse-grained and the all-atom models. Through this computational process, we are able to predict a picture of the IDP which is consistent with experimental results.
　Exhaustive sampling of protein conformation is generally difficult for conventional simulation techniques. We perform a multicanonical method for the conformational sampling: multicanonical molecular dynamics (McMD) simulation for the all-atom model, and multicanonical Monte Carlo (McMC) simulation for the coarse grained models. We produce the free-energy landscape at room temperature through the statistical analysis on the obtained simulation data. Furthermore, we are uncovering the molecular recognition mechanism of IDPs by comparing our results with those from experiment.