Transition networks for modeling the kinetics of conformational change in macromolecules

摘要

The kinetics and thermodynamics of complex transitions in biomolecules can be modeled in terms of a network of transitions between the relevant conformational substates. Such a transition network, which. overcomes the fundamental limitations of reaction-coordinate-based methods, can be constructed either based on the features of the energy landscape, or from molecular dynamics simulations. Energy-landscape-based networks are generated with the aid of automated path-optimization methods, and, using graph-theoretical adaptive methods, can now be constructed for large molecules such as proteins. Dynamics-based networks, also called Markov State Models, can be interpreted and adaptively improved using statistical concepts, such as the mean first passage time, reactive flux and sampling error analysis. This makes transition networks powerful tools for understanding large-scale conformational changes.