Protein Solutions
Calorimetry, Research and Consulting


Protein Solutions provides a range of scientific services such as assistance in experimental research, theory-based interpretation of data, as well as "know how" and consulting in protein/peptide stability and thermodynamics.

Upcoming Events

July 18, 2012

World Drug Target/Deliver Online Symposium Series

Past Events

2011

Lecture presentation at GE Healthcare meeting on label-free technology in Copenhagen University, Denmark

Lecture presentation at TA Instruments workshop and seminar at Roskilde University, Denmark

Published examples

Problem Titrations of several proteins with chitosan (a polysaccharide) reveal a bimodal reaction, where the initial stage is exothermic and the final stage is endothermic. This pattern is inconsistent with the “single set of multiple sites” binding model, where all interaction sites are similar.
Solution Analysis of the data with the McGhee-Von Hippel binding model allows interpretation of the bimodal character of the reaction. Combined with the additional clues from the DSC data, the results indicate that the favorable inter-protein interaction upon condensation on the polysacharide chain is necessary for the successful protein-chitosan particle formation.

  • Kasimova, M.R., Velázquez-Campoy, A., Nielsen, H.M. (2011). Biomacromolecules 12 (7), 2534-2543.

Problem The literature is full of experimental results giving inconsistent picture of α-crystallin stability, where different reports disagree on whether this protein is marginally or exceedingly stable.
Solution Combination of DSC and CD techniques can be used to compare the acid- and heat-induced denaturation of a α-crystallin, showing that unfolding of this protein is incomplete even at the extremes of temperature and acidity.

  • Rasmussen, T., Weert, M.v.d. and Kasimova, M.R. (2011). Proteins: Structure, Function, and Bioinformatics, 79, 1747-1758.

Problem A chaperone-like protein α-crystallin can be used to prevent fibrillation of insulin, indicating stabilization of insulin in solution. However, the thermal stability of insulin is not improved in presence of alpha-crystallin.
Solution A series of DSC experiments combined with CD and fluorescence reveal that α-crystallin promotes dissociation of insulin oligomers, resulting in conformations with lower degree of association and thus with lower thermal stability.

  • Rasmussen, T., Kasimova, M.R., Jiskoot, W., and Weert, M.v.d. (2009). Biochemistry, 48 (39), 9313–9320.

The use of ITC for the investigation of thermodynamics of binding of peptoids to liposomes.

  • Jing, X., Simonsen, A.H., Kasimova, M.R. Franzyk, H., Foged, C., Nielsen, H.M. (2010). Drug Discovery Today, 15 (23-24), 1109.
  • Nielsen, H.M., Jing, X., Simonsen, A.H., Kasimova, M.R. Malmsten, M., Franzyk, H., Foged, C. (2010). J. Pep. Sci., 16, 151.

The following two articles describe the use of ITC for the understanding of molecular mechanism of complex formation between siRNA and polyamidoamine dendrimers of different size and charge.

  • Jensen, L.B., Pavan, J.M., Kasimova, M.R., Rutherford, S., Danani, A., Nielsen, H.M., and Foged, C. (2011). Int. J. Pharm. 416, 410-418.
  • Jensen, L.B., Mortensen, K., Pavan, G.M., Kasimova, M.R., Jensen, D.K., Gadzhyeva, V., Nielsen, H.M., and Foged, C. (2010). Biomacromolecules, 11, 3571–3577.

Here, the ITC method is used for deciphering the molecular mechanism of interaction between ISCOM particles and lipid model systems.

  • Madsen, H,B,, Arboe-Andersen, H,M., Rozlosnik, N., Madsen, F., Ifversen, P., Kasimova, M.R. and Nielsen, H.M. (2010). BBA (Membranes), 1798 (9), 1779–1789.