LIFE SCIENCES

Prof. Dr. Holger Gohlke and Jesko Kaiser investigated the binding of resensitizers in the nicotinic acetylcholine receptor as a potential treatment option for nerve agent poisoning. They identified a potential allosteric binding site, explaining the experimentally observed effect on the receptor. Based on these results, the researchers identified novel analogs with improved properties and new lead structures with improved affinity compared to MB327, potentially acting as new starting points to ultimately close the gap in nerve agent poisoning treatment.

Chiral amines, a group of small chemicals, are central building blocks to a variety of fine chemical products. These include agrochemicals and pharmaceuticals such as Sitagliptin, a potent drug used to treat type II diabetes. Accordingly, biotech and pharmaceutical companies are highly interested in the efficient and sustainable production of these compounds. A group of enzymes already in use to fill this need are Transaminases (TAs). In this project, Prof. Dr. Gohlke and Steffen Docter investigated the thermal unfolding behavior of two sets of TA variants of fold type I and IV families of PLP-dependant enzymes by simulating rigid cluster decompositions using Constraint Network Analysis (CNA).

Life at the molecular level is driven by the interplay of many biomolecules. Much like man-made machines in everyday life, they need to move, rotate, react to signals or use and provide resources. Unlike man-made machines, however, they function at the atomic level so directly observing their workings is impossible as they are invisible both to the naked eye and regular optic microscopes. Specific highly specialised equipment can provide insight into the inner working of these atomic-sized machines, but such equipment is very expensive and the required wet-lab setups can be highly involved.

FitMultiCell is a computational pipeline developed by Prof. Dr.-Ing. Jan Hasenauer's team to tackle the complexity of simulating and fine-tuning biological tissues. This tool streamlines the creation, simulation, and calibration of biological models that imitate cellular interactions within tissues. The pipeline offers a user-friendly platform for researchers to conduct analyses on supercomputers like JUWELS. FitMultiCell's flexibility and power are demonstrated in studies on viral infections, tumor growth, and organ regeneration, proving its efficiency in refining models to match experimental data. Furthermore, enhancements for handling data outliers and scalability ensure FitMultiCell's robust application in diverse research fields.

Heinrich Heine University Researchers use JUWELS to study reactive metabolites in their pursuit of new biotechnological applications.

A research team led by Prof. Dr. Holger Gohlke at the Heinrich Heine University of Düsseldorf is a long-time user of the Jülich Supercomputing Centre’s (JSC’s) world-class high-performance computing infrastructure. The team has recently employed JSC’s JUWELS supercomputer to study a select class of enyzmes that play an outsized role in metabolizing chemical compounds coming from outside the body.

A research team at the Heidelberg Institute for Theoretical Studies and Heidelberg University is using the power of high-performance computing (HPC) to better understand how collagen—the most common protein in our body—transports shock and other forces toward its weakest molecular links, giving researchers deeper insight into understanding how collagen in tendons absorbs stress and how this can prevent larger injuries

A research team led by Prof. Holger Gohlke at the Heinrich Heine University Düsseldorf is using supercomputing resources at the Jülich Supercomputing Centre (JSC) to better understand so-called hyperpolarization-activated cyclic nucleotide–gated (HCN) channels, which serve as crucial ion channels in the membrane for controlling electric pulses in the brain and heart, among other fundamental processes in the body.

Using the JURECA supercomputer, a team of University of Cologne researchers led by Prof. Dr. Joseph Kambeitz is simulating biophysical processes in the brain in pursuit of better understanding what leads to schizophrenia in patients. 

A research team led by Prof. Dr. Holger Gohlke and Dr. Carlos Navarro-Retamal have been using the JUWELS supercomputer at the Jülich Supercomputing Centre (JSC) to better understand how plants respond to changes in their environment at a molecular level. Specifically, the team used JUWELs to simulate how the TPC protein—also prevalent in the human body—helps facilitate information sharing between different parts of a plant in responding to changes in temperature, light, or other conditions that can affect growth. In order to gain a fundamental understanding of the process, the researchers ran computationally intensive molecular dynamics simulations of up to 600,000 atoms.

A team of researchers led by Prof. Dr. Holger Gohlke and Till El Harrar have been using high-performance computing (HPC) resources at the Jülich Supercomputing Centre (JSC) to better understand how aqueous ionic liquids and seawater interact with enzymes relevant for a host of biotechnological applications. Recently, the team focused on how aqueous ionic liquids—reminiscent to molten salts, certain types of mineral-rich hydrothermal waters and the like—impact behavior of the enzymes Lipase A from Bacillus subtilis. The team published three papers on its research.

Zinc ions have shown antiviral properties, but a key issue for their use for antiviral therapy is its difficulty, as a divalent metal ion, to cross the cell membrane and thus reach its targets inside the cell. A variety of ligands, including the FDA approved drug chloroquine (CQ), form complexes with these ions have been proposed to assist zinc permeation, possibly promoting the combined beneficial action of both zinc ions and the drugs against the virus. Here, we studied the permeation of chloroquine and the interaction of the drug with zinc ions in aqueous solution. For the latter, we take advantage of highly scalable ab initio molecular dynamics simulations to explore the diverse coordination chemistry of zinc ions.

G-protein coupled receptors (GPCRs) are membrane proteins that transmit the effects of extracellular ligands to effect changes in the intracellular G-protein signaling system. Approximately 800 GPCRs are encoded in the human genome and approximately half of all marketed drugs target GPCRs. Crystal structures often deviate from the natural system: Proteins, especially membrane-bound ones, do not necessarily crystallize in their biologically active structures and the measures needed to obtain suitable GPCR crystals tend to increase the diversity between the natural environment and the crystal. It is within this context that molecular-dynamics simulations play a special role in GPCR research as a full-value complement to experimental studies.

Most biological functions are mediated by conformational changes and specific association of protein molecules. Atomistic simulations are ideal to study the molecular details of such systems. However, often the associated timescales are beyond the maximum simulation times that can be reached even on supercomputers. In this project, researchers developed and tested advanced sampling simulations to accelerate protein domain motions and association of partner molecules. These techniques allow to study domain motions and association of protein molecules on currently accessible time scales. They were successfully applied to study the Hsp90 chaperone protein and to several protein-protein and protein-peptide systems of biological importance.

The conformations of ubiquitin chains are crucial for the so-called ubiquitin code, i.e. the selective signaling of ubiquitylated proteins for different fates in the eukaryotic cellular system. Extensive molecular dynamics simulations at two resolution levels were carried out for ubiquitin di-, tri- and tetramers of all possible linkage types. Analyzing the resulting, exceedingly large high-dimensional data sets was made possible by combining highly efficient neural network based dimensionality reduction with density based clustering and a metric to compare conformational spaces. The so obtained conformational characteristics of ubiquitin chains could be correlated with linkage-type and chain-length dependent experimental observations.

GPCRs sit in the cell membrane and transmit signals from the outside of the cell to its interior. Currently, drugs targeting these receptors only work by mimicking ligands, i.e. they activate or inhibit the receptors by changing their conformation. If the GPCR adopts an active conformation, it can bind proteins on the intracellular side of the cellular membrane, which then transmit the signal inside the cell. In this study, we investigated how a protein that stops the GPCR from signaling, interacts with a prototypical GPCR. We discovered that specific lipids can modify how signals are transmitted by modifying the way of interaction between the GPCR and arrestin. In the future this could enable the discovery of a new kind of drugs for GPCRs.

Heat shock protein 90 (Hsp90) is a molecular chaperone essential for the folding and stabilization of a wide variety of client proteins in eukaryotes. Many of these processes are associated with cancer and other diseases, making Hsp90 an attractive drug target. Hsp90 is a highly flexible protein that can adopt a wide range of distinct conformational states, which in turn are tightly coupled to the enzyme’s ATPase activity. In this project, atomistic molecular dynamics simulations, free energy calculations, and hybrid quantum mechanics/classical mechanics simulations were performed on both monomeric and full-length dimeric Hsp90 models to probe how long-range effects in the global Hsp90 structure regulate ATP-binding and hydrolysis.

Complex I is the largest and most intricate respiratory enzyme, which couples the free energy released from quinone reduction to transfer protons across a biological membrane. Recent X-ray structures of bacterial and eukaryotic complex I have advanced our understanding of the enzyme’s function, but the mechanism of its long-range energy conversion remains unsolved. Here, we use atomistic molecular dynamics simulations and free energy calculations to study how the protonation state, hydration dynamics, and conformational dynamics of complex I regulate its proton pumping activity. Our simulations mimic transient states in the enzyme’s pumping cycle to draw a molecular picture of the protonation signals along the membrane domain of complex I.

Cells communicate with each other through biochemical as well as mechanical signals. Essential biological processes such as cell division are critically steered by the tension across the cell-cell contacts. Using extensive molecular dynamics simulations, scientists analyzed the underlying molecular principles of mechano-sensing at cell-cell contacts. These simulations can give first insights into how proteins present at the cell-cell contact change their structure and localization and thereby help to sense mechanical stimuli. The findings can help understanding the mechanisms by which tissues, e.g. skin, grow along the direction of pulling forces which were applied by adding virtual springs into the simulation system.

The approximately 800 G-protein coupled receptors (GPCRs) in the human genome regulate communication across cell walls. They are targeted by approximately 40% of all marketed drugs. The project uses molecular-dynamics (MD) simulations to investigate ligand binding and receptor activation processes in GPCRs. An activation index for Class A GPCRs has been developed from a series of µsec molecular-dynamics simulations and tested for 275 published X-ray structures.  Binding of the α-domain of G proteins to GPCRs has also been characterized in detail. Metadynamics simulations in conjunction with unbiased MD simulations demonstrated the effect of mutations on the GPCR-ligand interaction in the histamine H₁ receptor.

The proteasome is a large biomolecular complex responsible for protein degradation. Recent experimental data revealed that there is an allosteric communication between a core and regulatory parts of the proteasome. In the project, researchers have used atomistic simulations to study molecular details of the allosteric signal – in their study triggered by a covalent inhibitor. While the inhibitor causes only subtle structural changes, the proteasome-wide fluctuation changes may explain the self-regulation of the biomolecular machine.

Intramembrane proteases control the activity of membrane proteins and occur in all organisms. A prime example is g-secretase, cleaving the amyloid precursor protein, whose misprocessing is related to onset and progression of Alzheimer's disease. Since a protease's biological function depends on its substrate spectrum, it is essential to study the repertoire of natural substrates as well as determinants and mechanisms of substrate recognition and cleavage—which is the aim of this collaborative research project. Conformational flexibility of substrate and enzyme plays an essential role for recognition, complex formation and subsequent relaxation steps leading to cleavage and product release.

The development of novel sustainable biocatalytic processes requires systematic studies of the molecular interactions between enzymes, substrates, and solvents. Based on the HLRS HPC infrastructure, comprehensive molecular simulations were performed to investigate substrate binding in enzymatic reaction systems.

Diabetes reaches epidemic proportions with a major and growing economic impact on the society. An effective treatment requires atomic-level understanding of how insulin acts on cells. Using molecular dynamics simulations, an international team of researchers studied the process of insulin binding to its receptor and the resulting structural changes at atomic scale with cryogenic election microscopy and atomistic MD simulation. The results of these studies were recently published in the Journal of Cell Biology.

ATP synthase is an enzyme found in organisms ranging from primitive bacteria to some of the most complex lifeforms, such as humans. Its energetic efficiency is unrivalled, but not well understood. Researchers of Gdansk University of Technology have been using HPC to study this remarkable enzyme at a level of detail never seen before.

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.

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.

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.

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.

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.

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.

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.

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.

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…

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…

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…

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.

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.

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.

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 Aβ_9-40 amyloid fibrils.

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.

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.

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.

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.

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.

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.

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.

A team of scientists of the University of Jyväskylä in Finland leveraged the computing power of HLRS supercomputer Hermit with the aim to study the structure, surface chemistry and functionalization strategies of gold nanoclusters in water - having from a few tens to a few hundreds of gold atoms - and to research their interactions with enteroviruses.

In the rod cells of the eyes of vertebrates, a special protein, named Rhodopsin, is responsible for the detection of the light and is directly involved in the activation of the signaling cascade that triggers the nervous pulses of the retina. The deep understanding of the early mechanisms of light vision goes beyond the scientific interest as it is also an important issue for the rationalization of many retina diseases.

Protein kinases are the key enzymes that control most cellular activities. A kinase that fails to work properly can therefore cause severe damage to the organism, causing diverse diseases including cancer. It is therefore highly desirable to develop drugs that modulate the activity of specific protein kinases. Using the supercomputing infrastructure of the Leibniz Supercomputing Centre in Garching near Munich, a team of scientists set out to shed light on the effect of the SH2 domain on the intrinsic motions of the catalytic domain.

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.

The structural characterization of disordered proteins is an inherently under-determined problem: a small number of restraints are insufficient to uniquely define the conformations of a system with thousands of degrees of freedom. Molecular simulations, with their empirical force fields, can offer the additional information required to obtain conformational ensembles for disordered states of proteins. However, these simulations must contend with a massive sampling problem, which was successfully achieved by a team of scientists of the Max Planck Institute for Biophysical Chemistry in Göttingen using HPC system SuperMUC.

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…

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.

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. 

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.

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. 

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. 

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.

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.

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.

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.

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.

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.

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.

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.