Cooperative structural transitions induced by non-homogeneous intramolecular interactions in compact globular proteins.

Abstract:

:The role played by non-homogeneous interactions in stabilizing cooperative structural changes in proteins was investigated by exhaustive simulations of all compact conformations compatible with several well-defined globule-like shapes in three dimensions. Conformational free energies corresponding to the association of residues i and j were computed both for the unperturbed system, all subject to identical intramolecular interactions, and for the perturbed system in which a single pair of residues is probed by changing its interactions with an attractive or repulsive interaction. The high packing density leads to strong coupling between residues so that specific interactions between a given pair of residues are accompanied by considerable enthalpy changes. Relatively weak, about 1-2 kcal/mol, attractive interactions can exert a dramatic effect on the free energy distribution. Usually, central positions in the sequence most affect the conformational characteristics. Some of these interaction pairs appear to be capable of effecting major conformation transitions because of the high level of cooperativity in the dense state. Effects of repulsive interactions, however, do not depend so strongly on residue pair and cause more localized structural changes. This approach can suggest more, or less, sensitive loci for amino acid substitution.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Bahar I,Jernigan RL

doi

10.1016/s0006-3495(94)80798-2

subject

Has Abstract

pub_date

1994-02-01 00:00:00

pages

467-81

issue

2 Pt 1

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(94)80798-2

journal_volume

66

pub_type

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