Hierarchical organization of eglin c native state dynamics is shaped by competing direct and water-mediated interactions
- *Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290; and
- †Jordan High School, Durham, NC 27707
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Edited by Peter G. Wolynes, University of California at San Diego, La Jolla, CA, and approved May 30, 2008 (received for review February 25, 2008)
Abstract
The native state dynamics of the small globular serine protease inhibitor eglin c has been studied in a long 336 ns computer simulation in explicit solvent. We have elucidated the energy landscape explored during the course of the simulation by using Principal Component Analysis. We observe several basins in the energy landscape in which the system lingers for extended periods. Through an iterative process we have generated a tree-like hierarchy of states describing the observed dynamics. We observe a range of divergent contact types including salt bridges, hydrogen bonds, hydrophilic interactions, and hydrophobic interactions, pointing to the frustration between competing interactions. Additionally, we find evidence of competing water-mediated interactions. Divergence in water-mediated interactions may be found to supplement existing direct contacts, but they are also found to be independent of such changes. Water-mediated contacts facilitate interactions between residues of like charge as observed in the simulation. Our results provide insight into the complexity of the dynamic native state of a globular protein and directly probe the residual frustration in the native state.
Footnotes
- ‡To whom correspondence should be addressed. E-mail: gpapoian{at}unc.edu
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Author contributions: G.A.P. designed research; C.K.M. performed research; C.K.M. and C.C.G. analyzed data; and C.K.M. and G.A.P. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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See Commentary on page 10635.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0801850105/DCSupplemental.
- © 2008 by The National Academy of Sciences of the USA
