Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 13, Pages 4875-4880Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1116274109
Keywords
frustration; G(o)over-bar model; dynamically driven
Categories
Funding
- Pfizer, Inc.
Ask authors/readers for more resources
Allostery is a phenomenon that couples effector ligand binding at an allosteric site to a structural and/or dynamic change at a distant regulated site. To study an allosteric transition, we vary the size of the allosteric site and its interactions to construct a series of energy landscapes with pronounced minima corresponding to both the effector bound and unbound crystal structures. We use molecular dynamics to sample these landscapes. The degree of perturbation by the effector, modeled by the size of the allosteric site, provides an order parameter for allostery that allows us to determine how microscopic motions give rise to commonly discussed macroscopic mechanisms: (i) induced fit, (ii) population shift, and (iii) entropy driven. These mechanisms involve decreasing structural differences between the effector bound and unbound populations. A metric (ligand-induced cooperativity) can measure how cooperatively a given regulated site responds to effector binding and therefore what kind of allosteric mechanism is involved. We apply the model to three proteins with experimentally characterized transitions: (i) calmodulin-GFP Ca2+ sensor protein, (ii) maltose binding protein, and (iii) CSL transcription factor. Remarkably, the model is able to reproduce allosteric motion and predict coupling in a manner consistent with experiment.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available