Chapter 1 - The energy landscape perspective: cutting a Gordian knot

Abstract

In this introductory tutorial chapter the energy landscape perspective is described using an example that highlights the key techniques for sampling and calculation of observable properties. Exploring the landscape using methodology based on geometry optimisation, coarse-graining the landscape into local minima and the transition states that connect them, provides access to experimental time scales via well-defined approximations. Thermodynamic and kinetic properties are extracted using statistical mechanics and unimolecular rate theory. The theory and computational aspects of the landscape approach are illustrated for a protein containing a Gordian knot, which presents significant challenges in terms of structure prediction, thermodynamic properties, and folding pathways.