Mechanism of titin unfolding by force: insight from quasi-equilibrium molecular dynamics calculations.

Biophysical Journal
Germán Pabón, L Mario Amzel

Abstract

We have studied the unfolding by force of one of the immunoglobulin domains of the muscle protein titin using molecular dynamics simulations at 300 K. Previous studies, done at constant pulling rates, showed that under the effect of the force two strands connected to each other by six backbone H-bonds are pulled apart. No details about the mechanism of H-bond breaking were provided. Our simulation protocol "pull and wait" was designed to correspond to very slow pulling, more similar to the rates used in experiments than are the protocols used in previous computational studies. Under these conditions interstrand backbone H-bonds are not "ripped apart" by the application of the force. Instead, small elongations produced by the force weaken specific backbone H-bonds with respect to water-backbone H-bonds. These weakened bonds allow a single water molecule to make H-bonds to the CO and the NH of the same backbone H-bond while they are still bound to each other. The backbone H-bond then breaks (distance > 3.6 A), but its donor and acceptor atoms remain bound to the same water molecule. Further separation of the chains takes place when a second water molecule makes an H-bond with either the protein backbone donor or acceptor atom. Th...Continue Reading

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Dec 7, 2007·Pflügers Archiv : European journal of physiology·Wolfgang A Linke, Anika Grützner
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