Computational Biophysics Group

Welcome to the Computational Biophysics Group at Saarland University.

We develop methods related to molecular dynamics simulations, with the aim to understand the relationship between structure, dynamics, and function of biological macromolecules.

Prof. Dr. Jochen Hub
jochen dot hub at uni-saarland.de
+49 (0)681 302-2740
Campus E2 6, room 4.11
Office: Bettina Lau
b dot lau at mx.uni-saarland.de
+49 (0)681 302-2748
Campus E2 6, room 4.12

We have several interesting Bachelor and Master projects available. Find out more.

Research Topics

Biomembranes: structural transitions, lipid-protein interactions, and membrane complexity

The function of biological membranes goes far beyond the formation of a mere barrier. Membranes are subject to ongoing structural remodeling, which is controlled by interactions with proteins and by the lipid composition. We develop free energy calculation techniques to understand how membrane composition and interactions with proteins (such as viral fusion proteins) enable functionally important events at membranes including membrane fusion, pore formation, or drug permeation.

Biomembranes: structural transitions, lipid-protein interactions, and membrane complexity
Modeling and interpretation of X-ray scattering experiments with MD simulations

Collecting experimental data is often difficult – but the interpretation of the data may be even more challenging, for instance because the information content of the experimental signals is low. We develop methods for combining MD simulations with experimental data to get the best of two worlds, with some focus on small-angle X-ray and neutron scattering data (SAXS/SANS). Our developments involve accurate SAXS/SANS predictions, protein structure and ensemble refinement, studies on the protein hydration shell, and modeling of experiments at X-ray free electron lasers. We share our methods via the web server WAXSiS and GROMACS-SWAXS.

Modeling and interpretation of X-ray scattering experiments with MD simulations
Conformational dynamics of proteins

Proteins are not static building blocks but instead carry out their function –and malfunction– by structural transitions (Structure-function-dynamics relationship). We combine MD simulations with experiential data and enhanced-sampling techniques, to observe proteins while they function in atomic detail. Our portfolio comprises studies of molecular motors, protein-RNA/DNA complexes, membrane channels, and enzymes related to cancer progression.

Conformational dynamics of proteins

Latest Publications

MemPrep, a new technology for isolating organellar membranes provides fingerprints of lipid bilayer stress
MemPrep, a new technology for isolating organellar membranes provides fingerprints of lipid bilayer stress

Biological membranes have a stunning ability to adapt their composition in response to physiological stress and metabolic challenges. Little is known how such perturbations affect individual organelles in eukaryotic cells. Pioneering work provided insights into the subcellular distribution of lipids, but the composition of the endoplasmic reticulum (ER) membrane, which also crucially regulates lipid metabolism and the unfolded protein response, remained insufficiently characterized. Here we describe a method for purifying organellar membranes from yeast, MemPrep. We demonstrate the purity of our ER preparations by quantitative proteomics and document the general utility of MemPrep by isolating vacuolar membranes. Quantitative lipidomics establishes the lipid composition of the ER and the vacuolar membrane. Our findings have important implications for understanding the role of lipids in membrane protein insertion, folding, and their sorting along the secretory pathway. Application of the combined preparative and analytical platform to acutely stressed cells reveals dynamic ER membrane remodeling and establishes molecular fingerprints of lipid bilayer stress.

Molecular simulations reveal the free energy landscape and transition state of membrane electroporation
Molecular simulations reveal the free energy landscape and transition state of membrane electroporation

The formation of pores over lipid membranes by the application of electric fields, termed membrane electroporation, is widely used in biotechnology and medicine to deliver drugs, vaccines, or genes into living cells. Continuum models for describing the free energy landscape of membrane electroporation have been proposed decades ago, but they have never been tested against spatially detailed atomistic models. Using molecular dynamics (MD) simulations with a recently proposed reaction coordinate, we computed potentials of mean force of pore nucleation and pore expansion in lipid membranes at various transmembrane potentials. Whereas the free energies of pore expansion are compatible with previous continuum models, the experimentally important free energy barrier of pore nucleation is at variance with established models. We trace the discrepancy to previously incorrect assumptions on the geometry of the transition state; previous continuum models assumed the presence of a membrane-spanning defect throughout the process whereas, according to the MD simulations, the transition state of pore nucleation is typically passed before a transmembrane defect has formed. A modified continuum model is presented that qualitatively agrees with the MD simulations. Using kinetics of pore opening together with transition state theory, our free energies of pore nucleation are in excellent agreement with previous experimental data.

Meet the Team

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Noora Aho

Postdoc

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Joel Chavarria Rivera

Master student

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Jochen Hub

Professor of Computational Biophysics

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Bettina Lau

Secretary

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Johanna Linse

PhD student

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Mareike Oellers

Master student

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Leonhard Starke

PhD student

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Vasily Unguryan

PhD student

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Maciej Wójcik

Master student

Funding

Present and former