Stepan Timr

Stepan Timr
The Czech Academy of Sciences | AVCR · J. Heyrovský Institute of Physical Chemistry

PhD

About

27
Publications
4,091
Reads
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535
Citations
Citations since 2016
22 Research Items
499 Citations
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2016201720182019202020212022050100150
Introduction
I’m interested in the multi-scale modeling of protein diffusion and stability in crowded cell-like conditions. My research activities have also been connected with biological membranes: from molecular modeling of membrane fluorescent probes and mathematical analysis of two-photon polarization microscopy data to the description of membrane binding and conformational transitions of neuronal calcium sensor proteins.
Additional affiliations
May 2019 - April 2021
French National Centre for Scientific Research
Position
  • PostDoc Position
November 2017 - April 2019
French National Centre for Scientific Research
Position
  • PostDoc Position
June 2013 - September 2017
The Czech Academy of Sciences
Position
  • PhD Student
Education
October 2013 - September 2017
Charles University in Prague
Field of study
  • Biophysics, Chemical and Macromolecular Physics
October 2011 - May 2013
Charles University in Prague
Field of study
  • Biophysics and Chemical Physics
September 2008 - September 2011
Czech Technical University in Prague
Field of study
  • Mathematical Physics

Publications

Publications (27)
Article
Full-text available
The effect of macromolecular crowding on the stability of proteins can change with temperature. This dependence might reveal a delicate balance between two factors: the entropic excluded volume and the stability-modulating quinary interactions. Here we computationally investigate the thermal stability of the native state of chymotrypsin inhibitor 2...
Article
Full-text available
The thermal stability of the superoxide dismutase 1 protein in a crowded solution is investigated by performing enhanced sampling molecular simulations. By complementing thermal unfolding experiments done close to physiological conditions (200 mg/mL), we provide evidence that the presence of the protein crowder bovine serum albumin in different pac...
Article
In cells, proteins are embedded in a crowded environment that controls their properties via manifold avenues including weak protein-macromolecule interactions. A molecular level understanding of these quinary interactions and their contribution to protein stability, function and localization in the cell is central to modern structural biology. Usin...
Chapter
Proteins, in general, fold to a well-organized three-dimensional structure in order to function. The stability of this functional shape can be perturbed by external environmental conditions, such as temperature. Understanding the molecular factors underlying the resistance of proteins to the thermal stress has important consequences. First of all,...
Article
Full-text available
Recoverin is a neuronal calcium sensor involved in vision adaptation that reversibly associates with cellular membranes via its calcium-activated myristoyl switch. While experimental evidence shows that the myristoyl group significantly enhances membrane affinity of this protein, molecular details of the binding process are still under debate. Here...
Article
Full-text available
In this work, we investigate the β-barrel of superoxide dismutase 1 (SOD1) in a mutated form, the isoleucine 35 to alanine (I35A) mutant, commonly used as a model system to decipher the role of the full-length apoSOD1 protein in amyotrophic lateral sclerosis (ALS). It is known from experiments that the mutation reduces the stability of the SOD1 bar...
Article
Full-text available
Stress granules (SGs) are among the most studied membraneless organelles that form upon heat stress (HS) to sequester unfolded, misfolded, or aggregated protein, supporting protein quality control (PQC) clearance. The folding states that are primarily associated with SGs, as well as the function of the phase separated environment in adjusting the e...
Article
Full-text available
Fluorescence-detected linear dichroism microscopy allows observing various molecular processes in living cells, as well as obtaining quantitative information on orientation of fluorescent molecules associated with cellular features. Such information can provide insights into protein structure, aid in development of genetically encoded probes, and a...
Article
Protein misfolding and aggregation is observed in many amyloidogenic diseases affecting either the central nervous system or a variety of peripheral tissues. Structural and dynamic characterization of all species along the pathways from monomers to fibrils is challenging by experimental and computational means because they involve intrinsically dis...
Article
Full-text available
In this work we present the coupling between Dry Martini, an efficient implicit solvent coarse-grained model for lipids, and the Lattice Boltzmann Molecular Dynamics (LBMD) simulation technique in order to include naturally hydrodynamic interactions in implicit solvent simulations of lipid systems. After validating the implementation of the model,...
Article
Full-text available
Big Challenges on Joliot-Curie - Before it goes in full production, a series of Grand Challenges – large scale simulations from academic and industry research – were carried out on Joliot-Curie supercomputer, from June to September 2018, to check that the system is functioning properly. These Grand Challenges represent a unique opportunity for sele...
Article
Full-text available
We present a combination of force field and ab initio molecular dynamics simulations together with neutron scattering experiments with isotopic substitution that aim at characterizing ion hydration and pairing in aqueous calcium chloride and formate/acetate solutions. Benchmarking against neutron scattering data on concentrated solutions together w...
Article
The detailed functional mechanism of recoverin, which acts as a myristoyl switch at the rod outer-segment disk membrane, is elucidated by direct and replica-exchange molecular dynamics. In accord with NMR structural evidence and calcium binding essays, simulations point to the key role of enhanced calcium binding to the EF3 loop of the semi-open st...
Article
Full-text available
Two approaches for modeling of the transmembrane potential, as present in all eukaryotic cells, are examined in detail and compared with each other. One approach uses an externally applied electric field, whereas the other maintains an imbalance of ions on the two sides of a membrane. We demonstrate that both methods provide converged results conce...
Article
G protein-coupled receptors (GPCRs) and G proteins are key players of cellular signal transduction. They transduce signals from a multitude of extracellular stimuli into the cells. Despite a number of studies, many aspects of molecular mechanisms and spatiotemporal dynamics of G protein interactions with GPCRs remain unclear. In particular, it is u...
Article
Several methods based on single- and two-photon fluorescence detected linear dichroism have recently been used to determine the orientational distributions of fluorescent dyes in lipid membranes. However, these determinations relied on simplified descriptions of non-linear anisotropic properties of the dye molecules, using a transition dipole momen...
Article
Using replica exchange umbrella sampling we calculated free energy profiles for uptake of cholesterol and one of its oxysterols (7-ketocholesterol) from an aqueous solution into a high density lipoprotein particle. These atomistic molecular dynamics simulations show that both sterols are readily taken up from the aqueous solution with comparable fr...
Article
Orientation of lipophilic dye molecules within a biological membrane can report on the molecular environment, i.e., the physical and chemical properties of the surrounding membrane. This fact, however, remains underutilized, largely because of our limited quantitative knowledge of molecular orientational distributions and the fact that robust techn...
Article
Membrane proteins are a large, diverse group of proteins, serving a multitude of cellular functions. They are difficult to study because of their requirement of a lipid membrane for function. Here we show that two-photon polarization microscopy can take advantage of the cell membrane requirement to yield insights into membrane protein structure and...
Article
Full-text available
Expertomica Cells is a program for the creation and analysis of pedigree plots from time-lapse micrographs of cell monolayers. It enables recording the basic events in a cell cycle, cell neighbourhoods and spatial migration. The output is both numeric and graphical. The software helps to lower main hurdles in the manual analysis of cell monolayer d...

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Projects (2)
Archived project
Recoverin is a neuronal calcium sensing protein equipped with a calcium-induced myristoyl switch. We perform atomistic and coarse-grained molecular simulations to develop mechanistic understanding of the reversible membrane association of the protein with implications for its biological role.