We investigate the folding, binding and evolution of proteins using a computational approach that is largely based on simplified models of proteins. The models we use range from the simplest, two-dimensional HP (hydrophobic-polar) lattice models to more realistic models with various levels of coarse-graining. One of the most promising approaches is discrete molecular dynamics (DMD), which increases the time scale of molecular dynamics simulations by several orders of magnitude. The problems under study include folding, amyloid formation, the coupling between folding and binding, disorder-to-order transitions, and the evolution of protein structures from fragments corresponding to structural motifs.

The complement system plays a major role in innate immunity. It is capable of recognizing and eliminating invading pathogens and altered host cells through different activation routes. Our research activity is focused on the serine proteases of the complement system, and on their physiological inhibitor: C1-inhibitor. We use molecular biology, enzymology, X-ray crystallography and other physico-chemical methods to characterize the individual serine proteases and the C1-inhibitor, in order to reveal the mechanism of their action and control and to estimate their physiological significance in health and disease. 

Proteins and particularly enzymes are generally believed to be vulnerable structures sensitive to environmental changes, however, there are some exceptions. Extreme thermophilic microorganisms have an optimum growth temperature above 70 °C, while psychrophilic organisms are capable of living below 0 °C. Most enzymes isolated from thermophilic and psychrophilic sources are highly homologous in structure and function to those of mesophilic origin. The same building blocks, the same underlying physical principles and highly similar folds are used in these extremophilic enzymes. This observation raises the question: if heat resistant and cold tolerant proteins can also be constructed for a given function, using the same building elements and principles, why most enzymes work optimally at the edge of their stabilities.