Life Sciences Gauss Centre for Supercomputing e.V.

LIFE SCIENCES

Life Sciences

Principal Investigator: Ville R. I. Kaila, Technical University of Munich

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr84gu

In eukaryotes, conversion of foodstuff into electrochemical energy takes place in mitochondria by enzymes of the respiratory chain. Cytochrome c oxidase (CcO) reduces oxygen to water and pumps protons across the membrane. In this project, we elucidated how reduction of metal co-factors in CcO control the proton transfer dynamics. By combining atomistic MD simulations with hybrid QM/MM free energy calculations, we elucidated the location of a transient proton loading site near the active site, and identified how proton channels are activated during the different steps of the catalytic cycle.

Life Sciences

Principal Investigator: Jan Hasenauer, (1)Institute of Computational Biology, Helmholtz Zentrum München - German Research Center for Environmental Health, (2)Center for Mathematics, Technische Universität München, (3)Faculty of Mathematics and Natural Sciences, University of Bonn

HPC Platform used: SuperMUC and SuperMUC-NG of LRZ

Local Project ID: pr62li

Computational mechanistic modelling using systems of ordinary differential equations (ODE) has become an integral tool in systems biology. Parameters of such models are often not known in advance and need to be inferred from experimental data, which is computationally very expensive. The SuperMUC supercomputer enabled researchers from the Helmholtz Zentrum Munich to evaluate state-of-the-art algorithms and to develop novel, more efficient algorithms for parameter estimation from large datasets and relative measurements.

Life Sciences

Principal Investigator: Ville R. I. Kaila, Department of Chemistry, Technical University of Munich (Germany)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr74ve

Designing new enzymes is a grand challenge for modern biochemistry, and there are few examples for artificial enzymes with significant catalytic rate accelerations. We have developed a new method for computational enzyme design where we mimic evolution in nature and randomly mutate amino acids using a Metropolis Monte Carlo (MC) procedure. The aim of the method is to identify substitutions that increase the catalytic activity of enzymes. We probe the catalytic activity by quantum mechanics/classical mechanics (QM/MM) calculations, which are important for accurately modeling chemical reactions.

Life Sciences

Principal Investigator: Martin Zacharias, Lehrstuhl für Molekulardynamik, Physik-Department T38, Technische Universität München (Germany)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr74bi

Small GTPase protein molecules mediate cellular signaling events by transient binding to other proteins that in turn activate or deactivate processes in the cell. The signaling of GTPase proteins is mediated by switching between different active or inactive conformational states. Understanding the molecular details of these switching events is of great importance to understand cellular regulation and to design drug molecules to control cell functions. Using Molecular Dynamics advanced sampling techniques, the mechanism of conformational switching in the Rab8a-GTPase were investigated.

Life Sciences

Principal Investigator: Birgit Strodel, Forschungszentrum Jülich (Germany)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr74da

Amyloid-β (Aβ) peptide oligomers are the major contributing cause of neuronal death in Alzheimer’s disease. To understand how membrane lipids affect Aβ oligomerization, a system that includes six Aβ peptides and a membrane comprised of 1058 lipids was comprised to study these effects using molecular dynamics (MD) simulations. Hamiltonian replica-exchange molecular dynamics HREMD was employed to enhance the configurational sampling afforded by the MD protocol. The aim of this ongoing work is to see how the membrane lipids affect the conformation and morphology of the Aβ oligomers.

Life Sciences

Principal Investigator: Helmut Grubmüller, Max Planck Institute for Biophysical Chemistry, Göttingen (Germany)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr62de

The ribosome is a complex molecular machine which plays an essential role in protein biosynthesis across all domains of life. Knowing its structural and mechanistic details may help to develop new medical treatments by controlling protein production or to understand the context of neurodegenerative diseases. Using molecular dynamics simulations this project studies how certain nascent peptides, similar to particular antibiotics, affect the transport of produced polypeptide chains through the exit tunnel rendering this process moreover an attractive target from a pharmacological perspective.

Life Sciences

Principal Investigator: Ville R. I. Kaila, Technische Universität München (Germany)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr48de

Respiratory complex I is the largest and most intricate enzyme of the respiratory chain and responsible for converting energy from the reduction of quinone into an electrochemical proton gradient. The aim of the project is to identify key steps in the catalytic process during enzyme turnover, and to understand the mechanism of the long-range electrostatic coupling between sites located up to 200 Å apart. Large-scale Molecular Dynamics simulations of the entire enzyme enabled the exploration of different aspects of its function. These results provide both information on the redox coupling in complex I and how natural enzymes couple distal sites by propagation of electrostatic interactions.

Life Sciences

Principal Investigator: Alexandros Stamatakis, Heidelberg Institute for Theoretical Studies (Germany)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr58te

The field of phylogenetics reconstructs the evolutionary relationships among species based on DNA data. Substantial DNA sequencing technology advancements now generate a data avalanche. This allows using entire genomes of a large number of species for reconstructing phylogenetic trees. Statistical reconstruction approaches are widely used, but also highly compute-intensive. Researchers substantially improved the scalability and efficiency of two such statistical open-source tools on SuperMUC. In addition, they analysed several empirical large-scale datasets in collaboration with biologists.

Life Sciences

Principal Investigator: Michele Migliore, Consiglio Nazionale delle Ricerche (CNR), I.B.F. (Italy)

HPC Platform used: JUQUEEN of JSC

Local Project ID: PRA098

The main aim of this project was the development of the first detailed large-scale 3D model of the CA1 area of the hippocampus, a brain region well known for being involved in cognitive processes and deeply affected by aging and major brain diseases such as Alzheimer’s Disease and Epilepsy. Because of the current limitations in the experimental techniques, the cellular mechanisms underlying these processes remain relatively unknown. With our model, we maintain the 3D layout of the real system, and the neurons’ activity can be observed in exactly the same format as the in vivo recordings, with the fundamental advantage of being able to track network, cellular, and synaptic activity at any point of the network, and directly compare the...

Life Sciences

Principal Investigator: Martin Zacharias, Lehrstuhl für Molekulardynamik, Physik-Department T38, Technische Universität München (Germany)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr48po

The generation and assembly of Aβ peptides into pathological aggregates is associated with neurodegenerative diseases including Alzheimer’s disease. Goal of this project was to better understand the dynamics of γ-secretase a key enzyme for the formation of Aβ peptides using large scale Molecular Dynamics simulations and how it associates with substrate molecules. Using the HPC system SuperMUC it was possible to characterize local and global motions of γ-secretase in atomic detail and how it is related to function. In addition, large scale simulations were employed to investigate the amyloid propagation mechanism at the tip of an already formed amyloid fragment. The kinetics and thermodynamics of the process were analyzed and compared to...

Life Sciences

Principal Investigator: Helmut Grubmüller, Department of Theoretical and Computational Biophysics, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr48pa

Ion channels play a fundamental role in maintaining vital electrochemical gradients across the cell membrane and in enabling electrical signaling across cells. Key characteristics of ion channel function that can be experimentally quantified include ion permeation rates and selectivities. In this project, the functional mechanism of a very important class of ion channels is investigated with the help of molecular dynamics simulations. The computer simulations exhibit a wide range of GLIC states from completely closed to wide open, with conductance and selectivity for the open state in agreement with experimental values. The scientists are now beginning to investigate the intricate opening/closing mechanism in detail to ultimately explain it...

Life Sciences

Principal Investigator: Dieter Kranzlmüller(1) and Perter V. Coveney (2), (1) Ludwig-Maximilians-Universität, München (Germany), (2) Centre for Computational Science, University College London (UK)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr87be

Rapid and accurate calculation of binding free energies is of major concern in drug discovery and personalized medicine. A pan-European research team leveraged the computing power of LRZ’s SuperMUC system to predict the strength of macromolecular binding free energies of ligands to proteins. An in-house developed, highly automated, molecular-simulation-based free energy calculation workflow tool assisted the team in achieving optimal efficiency in its modelling and calculations, resulting in rapid, reliable, accurate and precise predictions of binding free energies.

Life Sciences

Principal Investigator: Helmut Grubmüller, Max-Planck-Institute for Biophysical Chemistry, Göttingen (Germany)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr84ma

HIV is one of the most significant global public health threats. The virus evolves rapidly, and multi-drug resistant strains have already emerged. The drugs approved to date target only four HIV proteins. While two novel drug targets, Rev and the capsid protein (CA), have been identified, so far none have reached clinical trials. Scientists leverage the computing power of HPC system SuperMUC to simulate detailed and accurate models of the protein-protein interactions of these targets with the aim to facilitate the design of more effective drugs.

Life Sciences

Principal Investigator: Christina Scharnagl and Dieter Langosch, Technical University of Munich (Germany)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr42ri

Integral membrane proteins exhibit conformational flexibility at different structural levels and time scales. Our work focusses on the biophysical basis of the interdependence of transmembrane helix dynamics, helix-helix recognition, and helix-lipid interactions. In this context, we try to understand the impacts of these phenomena on biological processes, such as membrane fusion, lipid translocation, and intramembrane proteolysis. Our approach closely connects experimental work and established computational analysis in order to interpret and guide the experiments and to validate the simulations.

Life Sciences

Principal Investigator: Martin Zacharias, Lehrstuhl für Molekulardynamik, Physik-Department T38, TU München (Germany)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr84ko

Leveraging the computing power of HPC system SuperMUC, researchers of the Technische Universität München investigated the free energy landscape for large-scale conformational changes coupled to the association of biomolecules. It allowed understanding the mechanism of substrate and inhibitor binding to the adenylate kinase (ADK) enzyme and helped to characterize the thermodynamics and kinetics of the propagation of Alzheimer Alzheimer Aβ9-40 amyloid fibrils.

Life Sciences

Principal Investigator: Frauke Gräter, Heidelberg Institute for Theoretical Studies (Germany)

HPC Platform used: Hornet of HLRS

Local Project ID: PP14102332

Composite materials made up of inorganic and biological matter present remarkable properties including fracture resistance, toughness and strength. A team of scientists of the Heidelberg Institute for Theoretical Studies has been investigating the mechanical properties of nacre, a material that possesses great stability due to its elaborate hierarchical nanostructures.

Life Sciences

Principal Investigator: Jürgen Pleiss, Institute of Technical Biochemistry, University of Stuttgart (Germany)

HPC Platform used: Hermit of HLRS

Local Project ID: Biocat

To gain further insight into how lipases catalyze the hydrolysis of water-insoluble triglycerides like fats and oils, scientists leveraged the computing power of the HLRS HPC infrastructure for a computational modelling of a lipase at a hydrophobic substrate interface. In total, more than 1μs of molecular dynamics simulations were performed on a system consisting of 100,000 atoms.

Life Sciences

Principal Investigator: Volkhard Helms, Center for Bioinformatics, Saarland University, Saarbrücken (Germany)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr58go

While some proteins of a biological cell are bound to cellular structures others diffuse freely. Especially in a crowded cellular environment, proteins constantly bump into other proteins which sometimes leads to biologically meaningful contact of the two proteins–the binding partners may either remain bound or a chemical reaction may take place. Performing atomistic molecular dynamics simulations on SuperMUC, bioinformaticists try to unravel the biophysical principles underlying such “specific” biomolecular interactions.

Life Sciences

Principal Investigator: Sabine Roller, Simulation Techniques and Scientific Computing, University of Siegen (Germany)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr85mu

Scientists leverage high performance computing technologies to identify the morphological characteristics of intracranial aneurysms that result in high frequency fluctuations, and assess the role of these fluctuations in aneurysmal wall degradation and consequently aneurysm rupture. Using SuperMUC they performed simulations with up to one billion elements, which allowed the simulation of flow at spatial and temporal resolutions of 8µm and 1µs, while resolving the smallest structures that can develop in a turbulent flow.

Life Sciences

Principal Investigator: Alexandros Stamatakis, Heidelberg Institute for Theoretical Studies

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr58te

Leveraging the computing capacities of HPC system SuperMUC, computer scientists conducted large-scale evolutionary analysis projects of birds and insects. Input datasets comprising 50-100 transcriptomes (the entirety of all RNA molecules in a genome) or genomes that represent the species under study requires supercomputers. Just computing the plausibility of a single out of trillions and trillions of possible evolutionary scenarios requires several terabytes of main memory, and billions of arithmetic operations are required.

Life Sciences

Principal Investigator: Ilpo Vattulainen, Department of Physics, Tampere University of Technology (Finland)

HPC Platform used: Hermit of HLRS

Local Project ID: PP12071362

Scientists from the Tampere University of Technology, Finland, have shown the profound importance of glycosylation in membrane receptor conformation. The researchers used extensive atomistic simulations together with biochemical experiments to show for EGFR that receptor conformation depends in a critical manner on its glycosylation.

Life Sciences

Principal Investigator: Marco Cecchini, ISIS, University of Strasbourg (France)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr89te

Ligand-gated ion channels (LGIC) play a central role in intercellular communication in the central and peripheral nervous systems as well as in non neuronal cells. Understanding their function at an atomic level of detail will be beneficial for the development of drug therapies against a range of diseases including Alzheimer's disease, schizophrenia, pain, and depression. By capitalizing on the increasing availability of high-resolution structures of both pentameric and trimeric LGICs we aim at elucidating the molecular mechanism underlying activation/deactivation by atomistic Molecular Dynamics (MD) simulations, which is essential to rationalize the design of potent allosteric modulators.

Life Sciences

Principal Investigator: Bert de Groot, Computational Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, Göttingen

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr85yi

Using Petascale system SuperMUC of the Leibniz Supercomputing Centre in Garching/Munich, scientists conducted simulations of mutated proteins to quantify and understand the mechanism of the change in population of binding compatible versus non-compatible states. This resulted in a predicted change in binding affinity which is a property that can be validated experimentally.

Life Sciences

Principal Investigator: Thomas Kühne, Institut für Physikalische Chemie, Johannes Gutenberg-Universität Mainz

HPC Platform used: JUQUEEN of JSC

Local Project ID: hmz32

Proteins are the workhorse molecules of life, which is due to their participation in essentially every structure and activity of life. However, in the absence of water as a solvent they lose their function in biological systems. The collection of one to two layers of interfacial water molecules surrounding proteins is generally referred to as “biological water”. The surface of a protein with its hydrophobic and hydrophilic amino acids is very complex, which makes it notoriously difficult to directly study its hydration dynamics experimentally. Instead, large-scale Molecular Dynamics (MD) simulations are a powerful tool to untangle the contributions originating from the various aspects of protein hydration and to obtain atomic-scale...

Life Sciences

Principal Investigator: Sabine Roller, University of Siegen

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr75du

A significant part of modern mortality is contributed by strokes, caused by the rupture of intracranial aneurysms (IA). Nearly 4-5% of the world population is reported to be suffering from IA. The deployment of a flow diverter stent in the parent artery of an aneurysm is a novel and minimally invasive treatment procedure, which can cause complete obliteration of the aneurysm by thrombosis.

Life Sciences

Principal Investigator: Martin Zacharias, Physik-Department T38, Technische Universität München

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr89tu

The process of protein-protein complex formation is of fundamental importance for a better understanding of a variety of biological processes. In a cellular environment the high concentration of surrounding proteins can influence the association process between proteins. Aim of the research project was to simulate the formation of specific and non-specific protein-protein complexes and to investigate the effect of additional protein molecules (crowding) on complex formation in atomic detail. 

Life Sciences

Principal Investigator: Matteo Dal Peraro, École Polytechnique Fédérale de Lausanne (Switzerland)

HPC Platform used: JUQUEEN of JSC

Local Project ID: PRA060

Bacterial infections represent the second leading cause of death worldwide. The effectiveness of the available weaponry against these pathogens is progressively lowered by the constant insurgence multidrug-resistant bacterial strains. Antibacterial resistance constitutes nowadays a major concern for human health due to its social implications and economical impact, i.e. loss of human lives and increased mortality, morbidity, hospitalization length and healthcare costs.

Life Sciences

Principal Investigator: Mark S.P. Sansom, University of Oxford (Great Britain)

HPC Platform used: Hermit of HLRS

Local Project ID: PP12061115

Membrane proteins are of great biomedical importance. They account for ~25% of all genes and are involved in diseases ranging from diabetes to cancer. Membrane proteins play a key role in the biology of infection by pathogens, including both bacteria and viruses. They also play an important role in signalling within and between cells. It is therefore not surprising that membrane proteins are major targets for a wide range of drugs and other therapeutic agents. Recently, the number of known structures of membrane proteins has started to increase. Large scale computer simulations allow researchers to study the movements of these proteins in their native membrane environments. 

Life Sciences

Principal Investigator: Piero Ugliengo, Department of Chemistry, University of Torino (Italy)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr86lre

The mechanisms of interaction between solid excipients and drugs are based on surface chemistry related phenomena. Consequently, understanding the physico-chemical features of surfaces is a fundamental step to describe and predict the strength of these interactions. The results of this analysis can shed light on how the nature of the excipient can affect the properties of a drug formulation. Among silica-based mesoporous materials, MCM-41 (Mobil Composition of Matter) is one of the most studied. In 2001 it was first proposed as a drug delivery system, with ibuprofen as a model drug. 

Life Sciences

Principal Investigator: Gerald Mathias, Lehrstuhl für BioMolekulare Optik, Ludwig-Maximilians-Universität München

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr89xe

Detailed knowledge about the structural and dynamical properties of biomolecules is essential for Life Sciences, from fundamental research to medical drug design. Molecular dynamics simulations are a valuable tool that complement experimental results and help to understand them. Molecular mechanics enable simulations of large systems, such as a protein in solution with several ten thousand atoms, up to a microsecond time scale. However, such simulations are by far not accurate enough for tasks like calculating infrared spectra. In contrast, high-level quantum mechanical methods like density functional theory provide the required accuracy, but are computationally limited to much smaller length and time scales.

Life Sciences

Principal Investigator: Helmut Grubmüller, Max-Planck-Institut für biophysikalische Chemie, Göttingen

HPC Platform used: SuperMUC of LRZ

Local Project ID: FG-nups

The nucleus of all eukaryotic cells is separated from the cytoplasm by the nuclear envelope. The passage of large macromolecules across the nuclear envelope is a tightly regulated process; the maintenance of the integrity of this barrier is crucial to cellular viability. Perforating the nuclear envelope are nuclear pore complexes (NPCs) through which large molecules are transported into and out of the nucleus.

Life Sciences

Principal Investigator: Frauke Gräter, Molecular Biomechanics - HITS gGmbH, Heidelberg (Germany)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr000ba

Using high-performance computer simulations and novel ways of analysing forces within proteins, a team of scientists of the Molecular Biomechanics Group at the Heidelberg Institute of Theoretical Studies (HITS) under leadership of Dr. Frauke Gräter analysed how the heat shock protein Hsp90, a helper protein vital to any cell in any organism, is switched by the binding of a small molecule.

Life Sciences

Principal Investigator: Nikolaus A. Adams, Lehrstuhl für Aerodynamik und Strömungsmechanik, Technische Universität München (Germany)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr28fa

Using HPC simulations, scientists are doing research on novel single-molecule manipulation techniques in biophysics and bio-nanotechnology to analyse the dynamics of the DNA macromolecule exposed to hydrodynamic flow and complex DNA-liquid interactions by numerical simulations.

Life Sciences

Principal Investigator: Wolfgang A. Wall, Institute for Computational Mechanics, Technische Universität München (Germany)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr32ne

Mechanical ventilation for patients suffering from lung diseases can lead to severe complications. Computer simulations contribute to gaining new insights into so called ventilation-induced lung injuries.

Life Sciences

Principal Investigator: Christina Scharnagl, Physics Department and ZNN/WSI, Technische Universität München (Germany)

HPC Platform used: SuperMUC of LRZ

Local Project ID: pr000cb

A team of scientists from Technische Universität München conduct molecular dynamics simulations on GCS HPC systems to probe the interactions of transmembrane domains, their structural dynamics, and their impact on the surrounding membrane.

Life Sciences

Principal Investigator: Andreas Lintermann, Fluid Mechanics and Institute of Aerodynamics, RWTH Aachen University (Germany)

HPC Platform used: Hermit of HLRS

Local Project ID: nose_sim

Medical professionals want supercomputing research to answer questions related to one of humanity’s most basic needs — breathing. Luckily, Andreas Lintermann and a group of researchers at RWTH Aachen University are employing computing resources at the High-Performance Computing Center Stuttgart (HLRS) to do just that.

Life Sciences

Principal Investigator: Dmitry Fedosov, Institute of Complex Systems (ICS-2), Research Center Juelich (Germany)

HPC Platform used: JUQUEEN of JSC

Blood performs a multitude of functions on its way through our body, from the transport of oxygen to the immune response after infections. In addition, the circulatory system may be also affected by injuries which cause bleeding, by the formation of plaques in arteries which cause coronary heart disease, and it provides the pathway for the organism invasion by bacteria or viruses. Thus, modeling of blood flow and its functions is an important challenge with many medical implications, but also with many interesting physical phenomena.

Life Sciences

Principal Investigator: Ralf Schneider, High Performance Computing Center Stuttgart (Germany)

HPC Platform used: Hermit of HLRS

Local Project ID: BoneImplant

The difference between a broken femur healing in several weeks and an entire hip replacement lies only millimeters apart. Researchers at GCS member centre HLRS (High Performance Computing Center Stuttgart) plan to use computation to make sure treating a broken leg bone in the future is not only precise, but also more personalized.