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

Scrutinizing the protein hydration shell from molecular dynamics simulations against consensus small-angle scattering data
Scrutinizing the protein hydration shell from molecular dynamics simulations against consensus small-angle scattering data

Biological macromolecules in solution are surrounded by a hydration shell, whose structure differs from the structure of bulk solvent. In crowded cellular environments, hydration shells constitute a large fraction of the overall solvent. While the importance of the hydration shell for numerous biological functions such as molecular recognition or enzymatic activity is widely acknowledged, it is poorly understood how the hydration shell is regulated by macromolecular shape and surface composition, mostly because a quantitative readout of the overall hydration shell structure has been missing. We show that small-angle scattering (SAS) in solution using X-rays (SAXS) or neutrons (SANS) provide a protein-specific footprint of the protein hydration shell that enables quantitative comparison with molecular dynamics (MD) simulations. By means of explicit-solvent SAS predictions, we derived the effect of the hydration shell contrast relative to bulk on the radii of gyration Rg of five proteins using 18 combinations of protein force field and water model. By comparing computed Rg values from SAXS relative to SANS in D2O with consensus experimental data from a worldwide round-robin study, we found that several but not all force fields yield a hydration shell contrast in remarkable agreement with experimental data. The hydration shell contrast, as captured by Rg values, strongly depends on the protein charge and geometric shape, thus providing a protein-specific footprint of protein–water interactions and a novel observable for scrutinizing atomistic hydration shell models against experimental data.

Molecular Simulations of Liquid Jet Explosions and Shock Waves Induced by X-Ray Free-Electron Lasers
Molecular Simulations of Liquid Jet Explosions and Shock Waves Induced by X-Ray Free-Electron Lasers

X-ray free-electron lasers (XFELs) produce x-ray pulses with high brilliance and short pulse duration. These properties enable structural investigations of biomolecular nanocrystals, and they allow one to resolve the dynamics of biomolecules down to the femtosecond timescale. Liquid jets are widely used to deliver samples into the XFEL beam. The impact of the x-ray pulse leads to vaporization and explosion of the liquid jet, while the expanding gas triggers the formation of shock wave trains traveling along the jet, which may affect biomolecular samples before they have been probed. Here, we used molecular dynamics simulations to reveal the structural dynamics of shock waves after an x-ray impact. Analysis of the density and temperature in the jet revealed shock waves that form close to the explosion center, travel along the jet with supersonic velocities, and decay exponentially with an attenuation length proportional to the jet diameter. A trailing shock wave formed after the first shock wave, similar to the shock wave trains in experiments. High shock wave velocities in our simulations are compatible with the phenomenon of “fast sound,” as emerging at large sound frequencies. Although using purely classical models in the simulations, the resulting explosion geometry and shock wave dynamics closely resemble experimental findings, and they highlight the importance of atomistic details for modeling shock wave attenuation.

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