Osmotic pressure induced coupling between cooperativity and stability of a helix-coil transition

Most helix-coil transition theories can be characterized by a set of three parameters: energetic, describing the (free) energy cost of forming a helical state in one repeating unit; entropic, accounting for the decrease of entropy due to the helical state formation; and geometric, indicating how many repeating units are affected by the formation of one helical state. Depending on their effect on the helix-coil transition, solvents or co-solutes can be classified with respect to their action on these parameters. Solvent interactions that alter the entropic cost of helix formation by their osmotic action can affect both the stability (transition temperature) and the cooperativity (transition interval) of the helix-coil transition. A consistent inclusion of osmotic pressure effects in a description of helix-coil transition for poly(L-glutamic acid) in solution with polyethylene glycol can offer an explanation of the experimentally observed linear dependence of transition temperature on osmotic pressure as well as the concurrent changes in the cooperativity of the transition.Comment: 5 pages, 3 figures. To be submitted to Phys.Rev.Let

Water reveals non-Arrhenius kinetics in protein folding experiments

Statistical theories describe systems in equilibrium, and cannot be used to study kinetics. However, the theo- ries are based on coarse-grained parameters, that include assumptions regarding the underlying kinetics. If such assumptions are incorrect, the theoretical expressions, used to process the experimental data, will not fit. I report on one such case we have met within the application of Zimm-Bragg [1] theory to process folding experiments, and discuss the reasons and consequences. Studies of relaxation phenomena in glass-forming liquids by default account for the shift in temperature by some value, corresponding to the glass formation temperature, .In particular, temperature shift appears in hydrated proteins because of the presence of partially glassy states giving rise to non- Arrhenius relaxation times log τ ~ [2]. A phenomenological approach was suggested by Adam and Gibbs as early as in 1965 to describe the sudden increase of viscosity and the slowing down of the collective modes in super-cooled liquids as the temperature is approaching[3]. The key idea of Adam-Gibbs theory was to consider the supercooled liquid as a set of clusters (cooperatively rearranging regions) of different sizes that change with temperature, giving rise to the shift in re- laxation time. The temperature shift factor is present in many theories describing properties of water. Thus, Truskett and Dill had to include the Adamm-Gibbs temperature shift into their simple analytical model of water to achieve the agreement with experimental data on the tem- perature dependence of self-diffusion coefficient [4]. Later, Schiro and Weik have summarised recent in vitro and in silico experimental results regarding the role of hydration water in the onset of protein structural dy- namics, and have reported the presence of super-Arrhenius relaxation region above the ”protein dynamic transition” temperature [4]. Recently, Mallamace et al have used the Adam-Gibbs theory in their NMR meas- urements of protein folding-unfolding in water [4] and to rationalise the complicated pressure-temperature diagrams in these glass-forming systems. Motivated by the considerations above, and taking into account the relationship between the unimolecular rate of folding in water and the relaxation time 45 , we introduce the tem- perature shift into the formulas used to fit experimental data on hydrated polypeptides. By doing so we resolve the paradox and complete the new method of processing the Circular Dichroism ex- perimental data on protein foldin

Differential scanning calorimetry of proteins and Zimm–Bragg model in water

Differential Scanning Calorimetry (DSC) is a regular and powerful tool to measure the specific heat profile of various materials. Hydrogen bonds play a crucial role in stabilizing the three-dimensional structure of proteins. Naturally, information about the strength of hydrogen bonds is contained in the measured DSC profiles. Despite its obvious importance, there is no approach that would allow the extraction of such information from the heat capacity measurements. In order to connect the measured profile to microscopic properties of a polypeptide chain, a proper model is required to fit. Using recent advances in the Zimm–Bragg (ZB) theory of protein folding in water, we propose a new and efficient algorithm to process the DSC experimental data and to extract the H-bonding energy among other relevant constants. Thus, for the randomly picked set of 33 proteins, we have found a quite narrow distribution of hydrogen bonding energies from 1 to 8 kJ/mol with the average energy of intra-protein hydrogen bonds kJ/mol and the average energy of water–protein bonds as kJ/mol. This is an important illustration of a tiny disbalance between the water–protein and intraprotein hydrogen bonds. Fitted values of the nucleation parameter belong to the range from 0.001 to 0.01, as expected. The reported method can be considered as complementary to the classical two-state approach and together with other parameters provides the protein–water and intraprotein H-bonding energies, not accessible within the two-state paradigm