The subject of the research project is to determine the effect of the solute donor group on the thermal stability of protein. Studies are focused on characterization of the destabilizing properties of urea analogues: thiourea (with the C=S group) and selenourea (with the C=Se group) in confrontation with the influence of urea (with the C=O group). Ultimately, they are to explain the mechanism of the impact of destabilizing solutes on the folded state of peptides and proteins. The thermal stability of hen egg lysozyme in the presence of urea analogues will be determined using differential scanning microcalorimetry (DSC). According to the experimental and theoretical premises known from the literature and my research, the effect of dissolved solutes on protein stability can be realized through interaction with water with properties modified by these solutes. It is therefore justified to search for the nature of these modifications using the experimental and computational techniques proposed in the project. For this purpose, I plan to obtain the energetic-structural characteristics of water molecules in the hydration spheres of these analogues. The effect on water structure will be investigated by means of the FTIR spectroscopy with an application of a technique of semi-heavy water (HDO) isotope dilution in ordinary water solution. I will analyze the spectral data using the "difference spectra method" which leads to the isolation of the solute-affected water spectrum. I will interpret the results of the analysis in the context of intermolecular interactions: structures occurring in the system, energy of hydrogen bonds and intermolecular distances between water molecules. In addition, to reveal the bands associated with ND vibrations of isotopically substituted amino groups of urea analogues, I will examine the hydration of N,N,N',N'-tetramethylthiourea. The interpretation of spectral results will be strengthened by theoretical calculations. The experimental and computational approach used in the project will allow to propose a coherent picture of the impact of urea analogues on the thermal stability of hen egg lysozyme. The anticipated research results will be a valuable contribution to knowledge of protein stability and will potentially have a practical application at the design stages of various biotechnological processes.