Introduction to protein folding for physicists

TL;DR

This paper introduces physicists to the protein folding problem, discussing its significance, current methods, and the physical principles and statistical mechanics used to understand the complex conformational space of proteins.

Contribution

It provides a comprehensive overview tailored for physicists, integrating scattered literature to facilitate understanding of protein folding from a physical perspective.

Findings

Summarizes the importance of the protein folding problem.

Reviews current methods and their physical basis.

Introduces statistical mechanics approaches to macromolecular phase spaces.

Abstract

The prediction of the three-dimensional native structure of proteins from the knowledge of their amino acid sequence, known as the protein folding problem, is one of the most important yet unsolved issues of modern science. Since the conformational behaviour of flexible molecules is nothing more than a complex physical problem, increasingly more physicists are moving into the study of protein systems, bringing with them powerful mathematical and computational tools, as well as the sharp intuition and deep images inherent to the physics discipline. This work attempts to facilitate the first steps of such a transition. In order to achieve this goal, we provide an exhaustive account of the reasons underlying the protein folding problem enormous relevance and summarize the present-day status of the methods aimed to solving it. We also provide an introduction to the particular structure of these biological heteropolymers, and we physically define the problem stating the assumptions behind this (commonly implicit) definition. Finally, we review the 'special flavor' of statistical mechanics that is typically used to study the astronomically large phase spaces of macromolecules. Throughout the whole work, much material that is found scattered in the literature has been put together here to improve comprehension and to serve as a handy reference.