Flexibility and critical hydrogen bonds in cytochrome c.

Michael Thorpe, B. M. Hespenheide, Y. Yang, L. A. Kuhn

Research output: Chapter in Book/Report/Conference proceedingChapter

13 Citations (Scopus)

Abstract

We show that protein flexibility can be characterized using graph theory, from a single protein conformation. Covalent and hydrogen bonds are modeled by distance and angular constraints, and a map is constructed of the regions in this network that are flexible or rigid, based on whether their dihedral bonds remain rotatable or are locked by other interactions in the network. This analysis takes only a second on a typical PC, and interatomic potentials; the most time-consuming aspect of molecular dynamics calculations, are not required. Our preliminary work has shown that this approach identifies the experimentally observed, biologically important flexible regions in HIV protease and lysine-arginine-ornithine binding protein. Here we analyze three evolutionarily distant cytochromes c, and find strong similarity between their flexible regions, despite having only 39% sequence identity. Furthermore, we show how the structural flexibility increases as the weaker hydrogen bonds are removed, as would happen under thermal denaturation of the protein. This approach identifies the critical hydrogen bonds that cross-link the tertiary structure.

Original languageEnglish (US)
Title of host publicationPacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
Pages191-202
Number of pages12
StatePublished - 2000
Externally publishedYes

Fingerprint

Cytochromes c
Hydrogen
HIV Protease
Protein Denaturation
Protein Conformation
Ornithine
Molecular Dynamics Simulation
Lysine
Arginine
Carrier Proteins
Hot Temperature
Proteins

Cite this

Thorpe, M., Hespenheide, B. M., Yang, Y., & Kuhn, L. A. (2000). Flexibility and critical hydrogen bonds in cytochrome c. In Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing (pp. 191-202)

Flexibility and critical hydrogen bonds in cytochrome c. / Thorpe, Michael; Hespenheide, B. M.; Yang, Y.; Kuhn, L. A.

Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing. 2000. p. 191-202.

Research output: Chapter in Book/Report/Conference proceedingChapter

Thorpe, M, Hespenheide, BM, Yang, Y & Kuhn, LA 2000, Flexibility and critical hydrogen bonds in cytochrome c. in Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing. pp. 191-202.
Thorpe M, Hespenheide BM, Yang Y, Kuhn LA. Flexibility and critical hydrogen bonds in cytochrome c. In Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing. 2000. p. 191-202
Thorpe, Michael ; Hespenheide, B. M. ; Yang, Y. ; Kuhn, L. A. / Flexibility and critical hydrogen bonds in cytochrome c. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing. 2000. pp. 191-202
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