Thermodynamics of Protein Folding

TL;DR

This paper provides an introductory overview of the thermodynamics involved in protein folding, emphasizing free energy, entropy, and enthalpy, and discusses computational techniques for analyzing protein structures.

Contribution

It offers a formal, thermodynamics-based foundation for understanding protein folding and dynamics, integrating concepts of free energy, entropy, and enthalpy with computational analysis methods.

Findings

Deeper understanding of free energy in protein folding

Analysis of temperature effects on folding landscape

Overview of computational techniques for structure analysis

Abstract

While many good textbooks are available on Protein Structure, Molecular Simulations, Thermodynamics and Bioinformatics methods in general, there is no good introductory level book for the field of Structural Bioinformatics. This book aims to give an introduction into Structural Bioinformatics, which is where the previous topics meet to explore three dimensional protein structures through computational analysis. We provide an overview of existing computational techniques, to validate, simulate, predict and analyse protein structures. More importantly, it will aim to provide practical knowledge about how and when to use such techniques. We will consider proteins from three major vantage points: Protein structure quantification, Protein structure prediction, and Protein simulation & dynamics. In the previous chapter, "Introduction to Protein Folding", we introduced the concept of free energy and the protein folding landscape. Here, we provide a deeper, more formal underpinning of free energy in terms of the entropy and enthalpy; to this end, we will first need to better define the meaning of equilibrium, entropy and enthalpy. When we understand these concepts, we will come back for a more quantitative explanation of protein folding and dynamics. We will discuss the influence of temperature on the free energy landscape, and the difference between microstates and macrostates.