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Research Project NCN Opus no. 2013/11/B/NZ1/02258

Protein stability in aqueous solutions of osmolytes studied through complementary theoretical and experimental approach

Principal Investigator: Prof. Dr. Janusz Stangret, D.Sc., Ph.D., B.E.

Project Summary

The goal of this project is to obtain an insight into the molecular mechanism through which osmolytes affect the structure and thermal stability of proteins, and the insight into the role of water molecules in this mechanism. The main goal of the project will be achieved if these partial objectives will be successfully finished: (1) characterization of the influence of various osmolytes on thermal stability of different proteins (by means of microcalorimetric method DSC); (2) characterization of the influence of these proteins and osmolytes on water structure by means of spectroscopic and computational methods (ab initio calculations and molecular dynamics simulations); (3) direct examination of the proposed models of osmolytic stabilization/destabilization at the microscopic level from ∆free energy profiles analysis of protein unfolding process, using molecular dynamics simulations.

Structural stability of biomolecules is a vital issue in today’s biotechnology and related branches of science and technology. The fragile equilibrium between native and denatured states of a biomolecule often determines its intrinsic ability to perform physiological functions. Its destruction may lead to unfavourable processes such as specific aggregation, which is the cause of many prion diseases (e.g. Creuzfeld-Jacob disease and many more). The possibility of easy stability modulation of biomolecules still seems to be largely unavailable to us, or remains a matter of chance. The subject of biomolecules stabilization (mainly protein stabilization) is for sure one of the most important issues of modern science. Combined results of experimental and computational studies on proteins stability and structure in water solutions of osmolytes will provide a valuable image of interactions in this kind of systems. All experiments and simulations were designed to verify the hypothesis and at the end to provide a comprehensive mechanism of osmolytes influence on stability of proteins.

Publications Containing Project Results

  1. M. Stasiulewicz, A. Panuszko, M. Śmiechowski, P. Bruździak, P. Maszota, J. Stangret. Effect of urea and glycine betaine on the hydration sphere of model molecules for the surface features of proteins. J. Mol. Liquids 2021, 324, 115090.
  2. P. Bruździak, A. Panuszko, B. Piotrowski, J. Stangret. Structural changes of a simple peptide—Trpzip-1—in aqueous solutions and the corresponding hydration phenomena under the influence of temperature. J. Mol. Liquids 2019, 277, 532–540.
  3. B. Adamczak, M. Kogut, J. Czub. Effect of osmolytes on the thermal stability of proteins: replica exchange simulations of Trp-cage in urea and betaine solutions. Phys. Chem. Chem. Phys. 2018, 20, 11174–11182.
  4. P. Bruździak, A. Panuszko, E. Kaczkowska, B. Piotrowski, A. Daghir, S. Demkowicz, J. Stangret. Taurine as a water structure breaker and protein stabilizer. Amino Acids 2018, 50, 125–140.
  5. B. Adamczak, M. Wieczór, M. Kogut, J. Stangret, J. Czub. Molecular basis of the osmolyte effect on protein stability: a lesson from the mechanical unfolding of lysozyme. Biochem. J. 2016, 473, 3705–3724.
  6. A. Panuszko, P. Bruździak, E. Kaczkowska, J. Stangret. General Mechanism of Osmolytes’ Influence on Protein Stability Irrespective of the Type of Osmolyte Cosolvent. J. Phys. Chem. B 2016, 120, 11159–11169.
  7. P. Bruździak, A. Panuszko, M. Jourdan, J. Stangret. Protein thermal stabilization in aqueous solutions of osmolytes. Acta Biochim. Pol. 2016, 63, 65–70.
  8. A. Panuszko, B. Adamczak, J. Czub, E. Gojło, J. Stangret. Hydration of amino acids: FTIR spectra and molecular dynamics studies. Amino Acids 2015, 47, 2265–2278.
  9. P. Bruździak, B. Adamczak, E. Kaczkowska, J. Czub, J. Stangret. Are stabilizing osmolytes preferentially excluded from the protein surface? FTIR and MD studies. Phys. Chem. Chem. Phys. 2015, 17, 23155–23164.

Conference Contributions

  1. M. Stasiulewicz, A. Panuszko, J. Stangret. Spectroscopic investigation of water structure around betaine. XIVth International Conference on Molecular Spectroscopy (ICMS 2017), Białka Tatrzańska, Poland, 2017.
  2. B. Piotrowski, A. Panuszko, S. Demkowicz, J. Stangret. Taurine hydration – a spectroscopic approach. XIVth International Conference on Molecular Spectroscopy (ICMS 2017), Białka Tatrzańska, Poland, 2017.
  3. P. Maszota, M. Śmiechowski. "Specjalna" woda w wodnych roztworach osmolitów. XLV Ogólnopolska Szkoła Chemii, Rozewie, Poland, 2017.
  4. P. Maszota, M. Śmiechowski. Hydratacja mocznika i 1,1-dimetylomocznika na podstawie symulacji metodą dynamiki molekularnej. XLIV Ogólnopolska Szkoła Chemii, Koszuty, Poland, 2016.
  5. M. Śmiechowski, P. Maszota, A. Panuszko, J. Stangret. Infrared spectra of solute-affected water in aqueous solutions of urea and its N-methyl derivatives – experiment vs simulations. 52nd Symposium on Theoretical Chemistry (STC 2016), Bochum, Germany, 2016.
  6. E. Kaczkowska, A. Daghir, P. Bruździak, J. Stangret. Taurine-lysozyme interactions – FTIR studies. 33rd European Congress on Molecular Spectroscopy (EUCMOS 2016), Szeged, Hungary, 2016.
  7. B. Adamczak, M. Wieczór, M. Kogut, J. Stangret, J. Czub. The origin of the effect of osmolytes on protein stability. 10th European Biophysics Congress (EBSA 2015), Drezno, Germany, 2015.
  8. B. Adamczak, M. Wieczór, J. Stangret, J. Czub. How does betaine stabilize the folded state of proteins? 58 Zjazd Naukowy Polskiego Towarzystwa Chemicznego, Gdańsk, Poland, 2015.