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. 1993 Oct 15;90(20):9547–9551. doi: 10.1073/pnas.90.20.9547

Simulation of the kinetics of ligand binding to a protein by molecular dynamics: geminate rebinding of nitric oxide to myoglobin.

O Schaad 1, H X Zhou 1, A Szabo 1, W A Eaton 1, E R Henry 1
PMCID: PMC47606  PMID: 8415739

Abstract

We have begun to use molecular dynamics to simulate the kinetics of nitric oxide rebinding to myoglobin after photodissociation. Rebinding was simulated using a potential function that switches smoothly between a nonbinding potential and a binding potential as a function of the position and orientation of the ligand, with no barrier arising from the crossing of potential surfaces of different electron spin. In 96 of 100 trajectories, the ligand rebound in < 15 ps. The kinetic progress curve was obtained by determining the time in each trajectory at which the ligand rebound and then calculating the fraction of unbound ligands as a function of time. The curve can be well reproduced by a simple model based on the dynamics of a Langevin particle moving on a one-dimensional potential of mean force calculated from nonreactive protein trajectories. The rate of escape from the energy well adjacent to the heme is in good agreement with the value calculated from experimental data, suggesting that a multiple-well model provides a plausible explanation for the nonexponential rebinding kinetics. A transition-state analysis suggests that protein conformational relaxation coupled to the displacement of the iron from the heme plane is an unlikely cause for the nonexponential rebinding of nitric oxide.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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