Significance of Knotted Structures for Function of Proteins and Nucleic Acids - September 17-21, 2014

Significance of Knotted Structures for Function of Proteins and Nucleic Acids

Thursday Abstracts

Knots and Slipknots in Proteins Kenneth Millett . University of California, Santa Barbara, Santa Barbara, USA.

The strict conservation of knotted and slipknotted features within protein families despite large sequence divergence suggests the possibility of an important physiological role and the utility of a deeper understanding of their spatial character vis-à-vis the entire structure in order to identify contributing evidence that can clarify their role. The “knotting fingerprint” has provided a foundational method by which to encode and assess these structures. Its generation and application to protein structures provide the principal foci of the presentation.

What Forces Drive Conformational Changes? Robert L. Jernigan , Jie Liu, Yuan Wang, Kejue Jia, Kannan Sankar. Iowa State University, Ames, USA.

There are now many conformational transitions known for proteins. In many cases the transition directions appear to be an intrinsic property of the structure itself, and this has been observed in many cases by the use of elastic network models. This approach is successful for transitions from open to closed forms in enzymes. However, the elastic models cannot describe the opposite transitions from closed to open forms. In such cases forces may be required to open a protein structure. If the protein is an enzyme and its chemical reaction is exothermic, then this could be the origin of the forces. Wherever ATP hydrolysis is involved, this seems likely. Meaningful dynamics information can be extracted from multiple experimental structures of the same, or closely related, proteins or RNAs. Usually only a few principal components dominate the motions of the structures, and these usually relate to the functional dynamics. This dynamics information provides strong evidence for the plasticity of protein and RNA structures, and also suggests that these structures almost always have a highly limited repertoire of motions. The variabilities of the internal distances among such a set of structures can be used to construct elastic models that represent well these variabilities. We are computing pathways for transitions from closed to open forms, by applying forces to elastic models, by generating structures with a Metropolis Monte Carlo method, using free energies for structural intermediates computed using our 4-body potentials and entropies from elastic network models.

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