How to extract hydrogen bonding energies from circular dichroism measurements of polypeptide solutions?

The temperature dependence of helicity degree is a final point for extracting data about the conformational transitions in proteins from the CD signal [1]. But it is also the starting point for extracting, processing and analyzing the properties of a particular protein [2]. All one needs is to fit experimental data to a proper model which accounts for the most relevant interactions in the system. In particular, water-protein and intra-protein hydrogen bonds dominate the behavior of proteins and a theoretical model describing such interactions is of vital importance. In my talk I will present a model of this kind, we have developed recently. We start from the microscopic Hamiltonian formulation of the polypeptide model in water and follow the usual Statistical Mechanics route from the model to partition function and to the thermodynamics. Using Mayer expansion and summation over the solvent degrees of freedom, the problem is shown to be equivalent to in vacuo model with some effective, temperature dependent interaction energy [3]. Estimated partition function leads to the expressions for the thermodynamic potentials and order parameter averages. The comparison (least-square fit) with the experimental data points from CD experiments on protein folding allows to extract the information on hydrogen bonding strengths, not available with the classical approach [4,5]. We have developed a free online tool [6], FitFoldData (https://fit-fold-data.ung.si/cd-fitting), which performs the above-mentioned procedure