The interior of a living cell is a highly crowded place—in fact, up to 40 % of the entire volume is filled by proteins and other biomolecules. This means that a protein molecule immersed in such a densely packed environment constantly bounces into other molecules and transiently binds to them before moving on to other interaction partners. We are only beginning to grasp how a myriad of tightly regulated metabolic and signaling pathways, making the cell a living entity, can emerge from this dense molecular soup.

As a research team at J. Heyrovský Institute of Physical Chemistry, we use computer simulations to understand how enzymes, which are protein molecules catalyzing chemical reactions that make up cell metabolism, function in the crowded cellular interior, that is, under conditions that are far from those commonly probed in test-tube experiments. In particular, we explore ways in which the local structure and dynamics of the intracellular environment, where enzymes have been observed to form dynamic assemblies, can modulate enzyme activities.

Our ambition is to develop a multi-scale computational framework, combining molecular dynamics simulations with mesoscopic and kinetic models, that will allow linking details of conformational changes in an enzyme molecule to the architecture of a dynamic enzyme assembly and, in turn, to changes in the flux through the entire metabolic pathway. The goal is to shed light on mechanisms that allow the cell to control the rates of chemical reactions occurring in its interior, an ability that is key for cell survival.



As a Marie Skłodowska-Curie postdoctoral fellow working on the CROWDY project in the research team led by Fabio Sterpone, I looked into how the crowded environment affects motions of proteins and how it alters the stability of their three-dimensional structures. To achieve this goal, I performed computer simulations—at various levels of resolution—allowing me to capture the behavior of hundreds of large biomolecules at the same time, but also to resolve atomistic details of their interactions.

Video from our Lattice Boltzmann Molecular Dynamics simulation of ~200 proteins mimicking the composition of the E. coli cytoplasm.

One of the proteins I have focused on is superoxide dismutase 1 (SOD1), a protein that is abundant inside human cells. Unfolding of its structure can cause the ALS disease, a severe neurological disorder which kills motor neurons. My simulations have provided insights into how the unfolding of SOD1 is influenced by the presence of other proteins, mimicking the situation inside a cell. This research has been done in collaboration with Simon Ebbinghaus Lab, specializing in in vivo measurements of protein stability.

Unfolding of the SOD1 protein as captured in our molecular dynamics simulation.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 840395.


During my PhD, I used molecular dynamics simulations to investigate the mechanism of recoverin. This signaling protein, which can be found inside photoreceptor cells of the retina, participates in a calcium-dependent regulation of the vision process. I looked into how changes in the conformation of recoverin affect its ability to bind calcium ions and how calcium-activated recoverin binds to the lipid membranes of photoreceptor cells.

Simulation showing how recoverin binds to a lipid membrane via a myristoyl anchor (red).


As part of my long-term collaboration with Josef Lazar Lab and with Hof Fluorescence Group, I performed molecular dynamics simulations of fluorescent dyes embedded in lipid membranes, and, using quantum-mechanical calculations, I evaluated how these fluorescent molecules absorb polarized light (via a single-photon and a two-photon process) in such environments. I also created procedures for experimental data analysis and interpretation, and, occasionally, I got to perform polarization microscopy experiments myself.

(Left) a fluorescent dye (F2N12S) embedded in a lipid membrane and (right) the calculated directionality of its two-photon absorption.