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http://dx.doi.org/10.5012/bkcs.2012.33.11.3597

Potential of Mean Force Simulation by Pulling a DNA Aptamer in Complex with Thrombin  

Yang, Changwon (Department of Chemistry and Institute of Functional Materials, Pusan National University)
Kim, Eunae (BK-21 Project Team, College of Pharmacy, Chosun University)
Pak, Youngshang (Department of Chemistry and Institute of Functional Materials, Pusan National University)
Publication Information
Bulletin of the Korean Chemical Society / v.33, no.11, 2012 , pp. 3597-3600 More about this Journal
Abstract
Thrombin binding aptamter (TBA-15) is a 15-mer guanine-rich oligonucleotide. This DNA apamer specifically binds to the thrombin protein involved in blood coagulation. Using extensive umbrella sampling molecular dynamics simulation method at all atom level, we investigated the potential of mean force (PMF) upon pulling the DNA aptamer from the binding mode of aptamer/thrombin complex. From this calculation, the free energy cost for a full dissociation of this aptamer/protein complex is 17 kcal/mol, indicating a substantial binding affinity of TBA-15. Interestingly, this PMF reveals noticeable plateau regions along the pulling coordinate. Possible structural changes of this complex in the plateau were investigated in details.
Keywords
TBA-15; Thrombin binding aptamer; Umbralla sampling; Potential of mean force;
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