Protein aggregation in salt solutions (Faculty of Chemistry and Chemical Technology, University of Ljubljana)

Authors: Miha Kastelic, Yurij V. Kalyuzhnyi, Barbara Hribar Lee, Ken A. Dill, Vojko Vlachy

Proteins are biological macromolecules essential to life. The molecules are prone to form clusters in a process called aggregation, and it may be desirable or undesirable in a given context. The consequence of aggregation may be a separation of the system into two liquid phases, differing in protein concentration. This is a necessary first step in protein crystallization and further isolation. On the other side, the process causes a problem in the formulation of biological drugs as well as in living organisms, where aggregation may cause condensation diseases, such as Alzheimer’s. Due to their complicated structure the behavior of proteins is generally very complex. Despite this, some of their properties can be predicted by relatively simple models.

The authors have proposed a model of the solution in which forces between protein molecules are directional and of short range. Molecules can be bonded to each other through binding sites on the surface. These bonding sites somehow mimic charges on the protein, including dipole and higher order terms in the multipole expansion. The latter feature turns out to be crucial in describing the thermodynamic properties. The model predicts the formation of chains and clusters as well as the coexistence region of two liquid phases in the case of lysozyme solutions. The model has a predicting power: by knowing the temperatures which designate the onset of aggregation, we can calculate the whole phase diagrams and some other quantities predicting protein crystallization. Based on these findings, we began an extensive experimental study on the stability of protein solutions.

Vir: Miha Kastelic, Yurij V. Kalyuzhnyi, Barbara Hribar-Lee, Ken A. Dill, Vojko Vlachy, Protein aggregation in salt solutions, Proc. Natl. Acad. Sci. USA, 112 (2015) 6766-6770.