Three-body correlations in protein folding: the origin of cooperativity

The success of the protein folding process requires that the peptide chain find a structure that ensures the survival of its intramolecular H-bonds. In this work, we identify and model how water is hindered from invading and destroying the intramolecular H-bonds: a three-body protective association...

Full description

Saved in:
Bibliographic Details
Published in:Physica A 2002-04, Vol.307 (1), p.235-259
Main Authors: Fernández, Ariel, Colubri, Andrés, Stephen Berry, R.
Format: Article
Language:English
Subjects:
Collapse-inducing nucleus
Folding topology
Protein folding
Ubiquitin
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The success of the protein folding process requires that the peptide chain find a structure that ensures the survival of its intramolecular H-bonds. In this work, we identify and model how water is hindered from invading and destroying the intramolecular H-bonds: a three-body protective association establishes itself when a hydrophobic residue approaches a pair of residues held by an amide–carbonyl H-bond. This proximity disrupts the water structure surrounding the backbone H-bond, driving water molecules away so they cannot solvate the backbone. These three-body contributions often compensate thermodynamically for concurrent two-body hydrophobic–polar mismatches. A previously-developed theoretical method to generate folding pathways is extended to reveal the role of three-residue correlations in stabilizing the collapse-inducing folding nucleus; successful computer runs exhibit their formation and how they protect and scaffold incipient secondary structure.
ISSN:0378-4371
1873-2119
DOI:10.1016/S0378-4371(01)00586-6