A similarity measure for partially folded proteins: Application to unfolded and native-like conformational fluctuations

Edgar Larios, Wei Y. Yang, K. Schulten, M. Gruebele

Research output: Contribution to journalArticlepeer-review

Abstract

Computing the root-mean-square deviation (RMSD) of a partially folded protein structure from the folded state requires the two structures to be translationally and rotationally aligned. We examine the constraint matrix L that preserves orthogonality of the rotation matrix during minimization of the RMSD. L is proportional to the sensitivity of the RMSD to the rotational alignment matrix. Its trace yields an isotropic reaction coordinate, while its off-diagonal matrix elements are related to the moment of inertia derivative tensor that encodes anisotropic information about the structure. We use L to compare λ-repressor fragment 6-85 (λ 6-85) to several partially folded structures obtained from molecular dynamics simulation (MD), and find that L as a reaction coordinate indeed encodes some information about protein topology. We also apply C α RMSD, L and tryptophan sidechain mobility as criteria for native state structural fluctuations of several λ 6-85 mutants. The mutants' denaturation curves and fluorescence quenching are measured experimentally for comparison. The results are in accord with a recent proposal that structural fluctuations near the chromophore can induce increased native state fluorescence or hyperfluorescence during unfolding of proteins.

Original languageEnglish (US)
Pages (from-to)217-225
Number of pages9
JournalChemical Physics
Volume307
Issue number2-3 SPEC.ISS.
DOIs
StatePublished - Dec 27 2004

ASJC Scopus subject areas

  • Physics and Astronomy(all)
  • Physical and Theoretical Chemistry

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