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Abstract: The Zimm-Bragg (ZB) model serves as a fundamental framework for elucidating conformational transitions in biopolymers, offering simplicity and efficacy in processing experimental data. This study provides a comprehensive review of the Zimm-Bragg model and its Hamiltonian formulation, with particular emphasis on incorporating water interactions and chain size effects into the computational framework. We propose a modified ZB model that accounts for water-polypeptide interactions, demonstrating its ability to describe phenomena such as cold denaturation and helix-coil transitions. In the realm of NanoBioTechnologies, the manipulation of short polypeptide chains is commonplace. Experimental investigation of these chains in vitro often relies on techniques like Circular Dichroism (CD) and timeresolved infrared spectroscopy. Determining interaction parameters necessitates processing the temperature dependence of the normalized degree of helicity through model fitting. Leveraging recent advancements in the Hamiltonian formulation of the Zimm and Bragg model, we explicitly incorporate chain length and solvent effects into the theoretical description. The resulting expression for helicity degree adeptly fits experimental data, yielding hydrogen bonding energies and nucleation parameter values consistent with field standards. Differential Scanning Calorimetry (DSC) stands as a potent tool for measuring the specific heat profile of materials, including proteins. However, relating the measured profile to microscopic properties requires a suitable model for fitting. We propose a novel algorithm for processing DSC experimental data based on the ZB theory of protein folding in water. This approach complements the classical two-state paradigm and provides insights into protein-water and intraprotein hydrogen bonding energies. An analytical expression for heat capacity, considering water interaction, is derived and successfully applied to fit numerous DSC experimental datasets reported in the literature. Additionally, we compare this approach with the classical two-state model, demonstrating its efficacy in fitting DSC data. Furthermore, we have developed and launched a free online tool for processing CD and DSC experimental data related to protein folding, aiming to support scientific research.
Keywords: Zimm-Bragg model, conformational transitions, helix-coil transitions, cold denaturation, circular dichroism, differential scanning calorimetry, protein folding, water-protein interaction, hydrogen bonding energy, degree of helicity, short polypeptide chains, protein heat capacity, protein data analysis, dissertations
Published in RUNG: 27.01.2025; Views: 733; Downloads: 13
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Abstract: During the past decade the experimental studies of biopolymer conformations have reached an unprecedented level of detailization and allow to study single molecules in vivo [1]. Processing of experimental data essentially relies on theoretical approaches to conformational transitions in biopolymers [2]. However, the models that are currently used, originate from the early 1960's and contain several unjustified assumptions, widely accepted at that time. Thus, the view on the conformational transitions in the polypeptides as a two-state process has very limited applicability because the all-or-none transition mechanism takes place only in short polypeptides with sizes comparable to the spatial correlation length; the original formulation of Zimm-Bragg model is phenomenological and does not allow for a microscopic model for water; the implicit consideration of the water-polypeptide interactions through the ansatz about the quadratic dependence of free energy difference on temperature can only be justified through the assumption of an ideal gas with a constant heat capacity. To get rid of these deficiencies, we augment the Hamiltonian formulation [3] of the Zimm-Bragg model [4] with the term describing the water-polypeptide interactions [5]. The analytical solution of the model results in a formula, ready to be fit to Circular Dichroism (CD) data for both heat and cold denaturation. On the example of several sets of experimental data we show, that our formula results in a significantly better fit, as compared to the existing approaches. Moreover, the application of our procedure allows to compare the strengths of inter- and intra-molecular H-bonds, an information, inaccessible before. References [1] I. König, A. Zarrine-Afsar, M. Aznauryan, A. Soranno, B. Wunderlich, F. Dingfelder, J. C. Stüber, A. Plückthun, D. Nettels, B. Schuler, (2015), Single-molecule spectroscopy of protein conformational dynamics in live eukaryotic cells/Nature Methods, 12, 773-779. [2] J. Seelig, H.-J. Schönfeld, (2016), Thermal protein unfolding by differential scanning calorimetry and circular dichroism spectroscopy. Two-state model versus sequential unfolding/Quarterly Reviews of Biophysics, 49, e9, 1-24. [3] A.V. Badasyan, A. Giacometti, Y. Sh. Mamasakhlisov, V. F. Morozov, A. S. Benight, (2010), Microscopic formulation of the Zimm-Bragg model for the helix-coil transition/Physical Review E, 81, 021921. [4] B. H. Zimm, J. K. Bragg, (1959), Theory of the Phase Transition between Helix and Random Coil in Polypeptide Chains/Journal of Chemical Physics, 31, 526. [5] A. Badasyan, Sh.A. Tonoyan, A. Giacometti, R. Podgornik, V.A. Parsegian, Y.Sh. Mamasakhlisov, V.F. Morozov, (2014), Unified description of solvent effects in the helix-coil transition/Physical Review E, 89, 022723. Corresponding author: Artem Badasyan (artem.badasyan@ung.si)
Keywords: Biopolymers, Circular Dichroism, Zimm-Bragg model, helix-coil transition.
Published in RUNG: 22.10.2018; Views: 5671; Downloads: 0
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