Open AccessDNA energy landscapes via calorimetric detection of microstate ensembles of metastable macrostates and triplet repeat diseases
Author(s) -
Jens Völker,
H. Klump,
Kenneth J. Breslauer
Publication year - 2008
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0810376105
Subject(s) - ministate , energy landscape , dna , protein folding , folding (dsp implementation) , allosteric regulation , nucleic acid , conformational ensembles , metastability , chemistry , biophysics , biology , molecular dynamics , computational chemistry , biochemistry , enzyme , organic chemistry , electroencephalography , neuroscience , electrical engineering , engineering
Biopolymers exhibit rough energy landscapes, thereby allowing biological processes to access a broad range of kinetic and thermodynamic states. In contrast to proteins, the energy landscapes of nucleic acids have been the subject of relatively few experimental investigations. In this study, we use calorimetric and spectroscopic observables to detect, resolve, and selectively enrich energetically discrete ensembles of microstates within metastable DNA structures. Our results are consistent with metastable, "native" DNA states being composed of an ensemble of discrete and kinetically stable microstates of differential stabilities, rather than exclusively being a single, discrete thermodynamic species. This conceptual construct is important for understanding the linkage between biopolymer conformational/configurational space and biological function, such as in protein folding, allosteric control of enzyme activity, RNA and DNA folding and function, DNA structure and biological regulation, etc. For the specific DNA sequences and structures studied here, the demonstration of discrete, kinetically stable microstates potentially has biological consequences for understanding the development and onset of DNA expansion and triplet repeat diseases.