Protein dynamics, thermal stability, and free-energy landscapes: a molecular dynamics investigation.
Proteins have a complex free-energy landscape because of their rich topology and the nature of their nonbonded interaction potential. This has important consequences because the roughness of the landscape affects the ease with which a chain folds and also determines the dynamic behavior of the folded structure, thus influencing its functional and stability properties. A detailed description of the free-energy landscape is therefore of paramount importance for a quantitative understanding of the relationships between structure, dynamics, stability, and functional behavior of proteins. The free-energy landscape of a protein is a high-dimensional hypersurface, difficult to rationalize. Therefore, achieving its detailed graphical representation in a way that goes beyond the familiar funnel-like free-energy model is still a big challenge. We describe here an approach based on global structural parameters that allows a two-dimensional representation of the free-energy landscape from simulated atomic trajectories. As shown in this and in the accompanying article, our representation of the landscape, combined with other conformational analyses, provides valuable information on its roughness and on how atomic trajectories evolve with time.
D000465:Algorithms; D003013:Clostridium / Q000378:metabolism*; D003196:Computer Graphics; D003198:Computer Simulation; D004735:Energy Transfer; D008958:Models, Molecular; D009038:Motion; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry; D020027:Pyrococcus furiosus / Q000378:metabolism*; D012416:Rubredoxins / Q000737:chemistry* / Q000145:classification; D013045:Species Specificity; D013696:Temperature; D014584:User-Computer Interface
D011506:Proteins; D012416:Rubredoxins