Introduction to protein folding for physicists

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.

53 pages, 18 figures, the figures are at a low resolution due to arXiv restrictions, for high-res figures, go to http://www.pabloechenique.com

References in corpus (6)

• Exact Solution of the Munoz-Eaton Model for Protein Folding
• Downhill versus two-state protein folding in a statistical mechanical model
• Efficient model chemistries for peptides. I. Split-valence Gaussian basis sets and the heterolevel approximation in RHF and MP2
• Definition of Systematic, Approximately Separable and Modular Internal Coordinates (SASMIC) for macromolecular simulation
• Explicit factorization of external coordinates in constrained Statistical Mechanics models
• Mean Field Approach for a Statistical Mechanical Model of Proteins

Cited by in corpus (9)

• A mathematical and computational review of Hartree-Fock SCF methods in Quantum Chemistry
• Protofold II: Enhanced Model and Implementation for Kinetostatic Protein Folding
• Efficient model chemistries for peptides. I. Split-valence Gaussian basis sets and the heterolevel approximation in RHF and MP2
• A solvable model of the genesis of amino-acid sequences via coupled dynamics of folding and slow genetic variation
• The canonical equilibrium of constrained molecular models
• Exact and efficient calculation of Lagrange multipliers in constrained biological polymers: Proteins and nucleic acids as example cases
• An exact expression to calculate the derivatives of position-dependent observables in molecular simulations with flexible constraints
• Remark on Protein Collapse from a Random Walk
• Exact and efficient calculation of derivatives of Lagrange multipliers for molecular dynamic simulations of biological molecules