PhD study/position: Effect of lipid asymmetry on membrane protein function

Supervisor: Prof. RNDr. Robert Vácha, Ph.D.

Annotation

Eukaryotic and prokaryotic plasma membranes exhibit inherent asymmetry, with distinct lipid compositions between the two leaflets. However, most studies to date have focused on symmetric bilayers. This project addresses this gap by integrating molecular dynamics simulations with experimental techniques such as solid-state NMR spectroscopy and scattering methods. The primary aim is to elucidate the structural and dynamical properties of lipids in asymmetric membranes, particularly their interactions with integral membrane proteins, with an emphasis on bacterial lipid compositions. Initial step will involve determining lipid chain order parameters, bilayer structure, and lipid dynamics. Subsequently, lipid-protein interactions will be assessed, focusing on lipid-induced modulation of enzymatic activity in two bacterial proteins: OmpLA, a β-barrel protein, and GlpG, an α-helical transmembrane protein. The findings will offer key insights into the role of lipid asymmetry in biological membranes and its influence on membrane protein function, with potential applications in the development of lipid-targeted therapeutics and biosensors for pharmaceutical and biotechnological use.

Recommended literature

• Bartoš, L., Vácha, R.: Biophys. J. 2024, 123, 1-10
• M. Bogdanov, K. Pyrshev, S. Yesylevskyy, S., Ryabichko, V. Boiko, P. Ivanchenko, R. Kiyamova, Z. Q. Guan, C. Ramseyer, W. Dowhan, Sci. Adv. 2020, 6.
• G. J. Schutz, G. Pabst, Bioessays 2023, e2300116
• M. Varma, M. Deserno, Biophys. J. 2022, 121, 4001-4018

Research area: Computational biophysics

Funding of the PhD candidate: Wave grant

Current group: 8 postdocs, 6 PhD students,1 Master student, 3 technicians

Current projects are: National Institute of Virology and Bacteriology and ERC consolidator grant

Recent publications:

• Hazrati, M.K.; Vácha, R.: Membrane Adsorption Enhances Translocation of Antimicrobial Peptide Buforin 2. The Journal of Physical Chemistry B 2024, 128, 35, 8469–847
• Deb, R.; Torres, M.D.T.; Boudný, M.; Koběrská, M.; Cappiello, F.; Popper, M.; Dvořáková Bendová, K.; Drabinová, M.; Hanáčková, A.; Jeannot, K.; Petřík, M.; Mangoni, M.L.; Balíková Novotná, G.; Mráz, M.; de la
• Fuente-Nunez, C.; Vácha, R.: Computational Design of Pore-Forming Peptides with Potent Antimicrobial and Anticancer Activities. Journal of Medicinal Chemistry 2024, 67, 16, 14040–14061
• Blasco S.; Sukeník, L.; Vácha, R.: Nanoparticle induced fusion of lipid membranes. Nanoscale 2024, 16, 10221-10229
• Bartoš, L.; Drabinová, M.; Vácha, R.: Optimizing properties of translocation-enhancing transmembrane proteins. Biophysical Journal 2024, 123, 1–13
• Biriukov, D.; Vácha, R.: Pathways to a Shiny Future: Building the Foundation for Computational Physical Chemistry and Biophysics in 2050. ACS Physical Chemistry Au, 4(4), 302-313
• Morton, W.; Vácha, R.; Angioletti-Uberti, S.: Valency of Ligand–Receptor Binding from Pair Potentials. Journal of Chemical Theory and Computation 2024, 20, 7, 2901–2907
• Bartoš, L.; Vácha, R.: Peptide translocation across asymmetric phospholipid membranes. Biophysical Journal 2024, 123, 1-10
• Bartoš, L.; Menon, A.K.; Vácha, R.: Insertases Scramble Lipids: Molecular Simulations of MTCH2. Structure 2024, 32, 4, 505-510
• Pajtinka, P.; Vácha, R.: Amphipathic Helices Can Sense Both Positive and Negative Curvatures of Lipid Membranes. The Journal of Physical Chemistry Letters 2024, 15, 175−179
• Jahn, H.; Bartoš, L.; Dearden, G.I.; Dittman, J.S.; Holthuis, J.C.M.; Vácha, R.; Menon, A.K.: Phospholipids are imported into mitochondria by VDAC, a dimeric beta barrel scramblase. Nature Communications 2023, 14, 8115

More info: https://vacha.ceitec.cz

Outstanding candidates with experience in computer simulations and with an MSc/PhD degree in the fields of biophysics, soft matter physics, physical chemistry, computational chemistry, statistical mechanics, or related fields.

Experience with molecular dynamics simulations (with GROMACS, CHARMM, NAMD, AMBER, LAMMPS, etc.) at the atomistic or coarse-grained level would be an advantage.