Understanding Protein Folding Using Markov State Models

Abstract

Computer simulations are a powerful way of understanding molecular systems, especially those that are difficult to probe experimentally. How ever, to fully realize their potential, we need methods that can provide understanding, make a quantitative connection with experiment, and drive efficient simulations. The main purpose of this book is to introduce Markov state models (MSMs) and demonstrate that they meet all three of these requirements. In short, MSMs are network models that provide a map of the free energy landscape that ultimately determines a molecule’s structure and dynamics. These maps can be used to understand a system, predict experiments, or decide where to run new simulations to refine themap. Protein folding and function will often be used to illustrate the prin- ciples in this book as these problems have largely driven the development of MSMs; however, the methods are equally applicable to other molecu- lar systems and possibly entirely different prob- lems. Whether you are an experimentalist inter- ested in understanding a bit of theory and how it could complement your work or a theorist seek- ing to understand the details of thesemethods,we hope this book will be useful to you. This introduction provides a brief overview of the background leading to the development of MSMs, what MSMs are, and the contents of this book.