Introduction to Protein Folding

TL;DR

This paper introduces the fundamental concepts of protein folding, including physical and chemical factors, states along the folding pathway, and the dynamic nature of folding and unfolding processes, serving as an educational foundation.

Contribution

It provides an accessible overview of protein folding principles, emphasizing the stochastic process and factors influencing stability, aimed at beginners in Structural Bioinformatics.

Findings

Protein folding involves hydrophobic effects and backbone entropy.

Proteins can exist in multiple states, including disordered and aggregated forms.

Folding is a stochastic process influenced by temperature.

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 this chapter we explore basic physical and chemical concepts required to understand protein folding. We introduce major (de)stabilising factors of folded protein structures such as the hydrophobic effect and backbone entropy. In addition, we consider different states along the folding pathway, as well as natively disordered proteins and aggregated protein states. In this chapter, an intuitive understanding is provided about the protein folding process, to prepare for the next chapter on the thermodynamics of protein folding. In particular, it is emphasized that protein folding is a stochastic process and that proteins unfold and refold in a dynamic equilibrium. The effect of temperature on the stability of the folded and unfolded states is also explained.