Monte carlo simulations of biomolecular binding
Abstract
The intrinsic plasticity and functional disorder-order folding transitions upon binding can provide an important prerequisite in effective molecular recognition of unstructured proteins, including the ability to bind with several targets and the increased rates of specific macromolecular association. A microscopic study of coupling between folding and binding is conducted for the p27 protein which derives a kinetic advantage from its intrinsically disordered unbound form during binding to the tertiary complex. Hierarchy of structural loss during p27 protein coupled unfolding and unbinding is simulated using high--temperature Monte Carlo simulations initiated from the crystal structure of the tertiary complex. Subsequent determination of the transition state ensemble leads to an atomic picture of the binding mechanism in agreement with the experimental data. We show that a functionally important disorder-order folding transition coupled to binding is largely determined by the intermolecular requirements to form a specific complex that ultimately dictates the folding mechanism.
- Publication:
-
APS March Meeting Abstracts
- Pub Date:
- March 2003
- Bibcode:
- 2003APS..MAR.x9003V