Periodic and stochastic thermal modulation of protein folding kinetics

• Published in: The Journal of chemical physics Vol. 141; no. 3; p. 035103
• Main Authors: Platkov, Max, Gruebele, Martin
• Format: Journal Article
• Language: English
• Published: United States American Institute of Physics 21.07.2014
• Subjects: Chemical compounds; Chemical reactions; DETECTION; Energy transfer; ENZYMES; FLUCTUATIONS; FLUORESCENCE; Fluorescence Resonance Energy Transfer; Folding; INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; Kinases; Kinetics; Models, Molecular; Modulation; MOLECULES; Noise; Organic chemistry; PERIODICITY; Phosphoglycerate Kinase - chemistry; Physics; Protein Folding; Protein Unfolding; Proteins; REACTION KINETICS; Stochastic Processes; Stochastic resonance; Temperature; Thermal noise; Variation; WAVE FORMS; Waveforms
• ISSN: 0021-9606; 1089-7690; 1089-7690
• DOI: 10.1063/1.4887360

Chemical reactions are usually observed either by relaxation of a bulk sample after applying a sudden external perturbation, or by intrinsic fluctuations of a few molecules. Here we show that the two ideas can be combined to measure protein folding kinetics, either by periodic thermal modulation, or by creating artificial thermal noise that greatly exceeds natural thermal fluctuations. We study the folding reaction of the enzyme phosphoglycerate kinase driven by periodic temperature waveforms. As the temperature waveform unfolds and refolds the protein, its fluorescence color changes due to FRET (Förster resonant Energy Transfer) of two donor/acceptor fluorophores labeling the protein. We adapt a simple model of periodically driven kinetics that nicely fits the data at all temperatures and driving frequencies: The phase shifts of the periodic donor and acceptor fluorescence signals as a function of driving frequency reveal reaction rates. We also drive the reaction with stochastic temperature waveforms that produce thermal fluctuations much greater than natural fluctuations in the bulk. Such artificial thermal noise allows the recovery of weak underlying signals due to protein folding kinetics. This opens up the possibility for future detection of a stochastic resonance for protein folding subject to noise with controllable amplitude.