BIOPHYSICAL THEORY AND MODELING |
Molecular Dynamics Simulations of Trichomonas vaginalis Ferredoxin Show Loop-Cap Transition
Tiffany E. Weksberg 1, Lynch Gillian 2, Kurt Krause 3 and B Montgomery Pettitt 2*
1 Baylor College of Medicine
2 University of Houston
3 University of Otago
* To whom correspondence should be addressed. E-mail: pettitt{at}uh.edu.
Submitted on April 27, 2006
Revised on June 27, 2006
Accepted on 27 November 2006
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Abstract |
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The crystal structure of the oxidized Trichomonas vaginalis ferredoxin (Tvfd) showed a unique crevice that exposed the redox center. Here we have examined the dynamics and solvation of the active site of Tvfd using molecular dynamics simulations of both the reduced and oxidized states. The oxidized simulation stays true to the crystal form with a heavy atom RMSD of 2Å. However, within the reduced simulation of Tvfd a profound loop-cap transition into the redox center occurred within 6 nanoseconds of the start of the simulation and remained open throughout the rest of the 20 nanosecond simulation. This large opening seen in the simulations supports the hypothesis that the exceptionally fast electron transfer rate between Tvfd and the drug metronidazole is due to the increased access of the antibiotic to the redox center of the protein and not due to the reduction potential.
Key Words:
Molecular dynamics, Trichomonas vaginalis ferredoxin, metronidazole, simulation
