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Manual Modeling Solvent Environments: Applications to Simulations of Biomolecules

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Contributor Feig, Michael. Bibliography Includes bibliographical references and index. Throughout, the emphasis is placed on the application of such models in simulation studies of biological processes, although the coverage is sufficiently broad to extend to other systems as well. As such, this monograph treats a full range of topics, from statistical mechanics-based approaches to popular mean field formalisms, coarse-grained solvent models, more established explicit, fully atomic solvent models, and recent advances in applying ab initio methods for modeling solvent properties.

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When purchasing on PriceCheck's Marketplace buy clicking the Add to Cart button, the quantity limit of the product on offer is dependent on the stock levels as set by the shop. The shop is also responsible for any discounts they wish to offer. Subscribe to our newsletter. You're not signed in. Furthermore, our obtained structure will serve as a starting point for structure-guided drug discovery, developing the proteasome as a crucial drug target.

More information about our proteasome projects is available on our proteasome website. Easy access to our modeling techniques is provided through QwikMD , which was employed here for the first time. Our lungs are coated with a layer of protein and lipid mixture called lung surfactant, which prevents the lungs from collapsing and protects us from bacterial and viral infections see October and January highlights. Lung surfactant protein A SP-A - the major protein constituent of lung surfactant - plays a dual role. It aggregates DPPC lipid, a major component of lung membrane, into a lattice-like structure that prevents the lungs from collapsing.

SP-A is also known to recognize and bind bacterial lipids, namely lipid A, on surfaces of gram-negative bacteria, thereby helping to initiate various clearance mechanisms. However, it was unclear how SP-A exhibits such functional duality with its binding to two different types of lipids. Simulations have also revealed that SP-A binds stronger to bacterial lipid lipid A than to surfactant lipid DPPC lipid , which suggests SP-A may prioritize its host defense functions by transferring from lung membrane to bacterial surface.

These findings in atomistic detail will enable experimentalists to enhance the antimicrobial function of SP-A. More on our lung surfactant protein website. Virus capsids, specialized protein shells that encase the genome of viral pathogens, play critical roles in regulating viral infection, and are, thus, of great pharmacological interest as drug targets. In particular, small-molecule drugs typically Perspective applying simulations in NAMD to study drug-bound hepatitis B virus HBV and human immunodeficiency virus type 1 HIV-1 capsids suggests the types of valuable chemical and physical information computational approaches can reveal, and underscores the importance of simulating, not isolated capsid proteins, but functional assemblies up to the level of complete capsids.

Notably, through analysis with VMD , the study found that binding of the drug HAP1 to the HBV capsid causes global structural changes that subtly alter the overall capsid shape, including a flattening of capsid curvature. Further, the study found that the binding of the drug PF74 to the HIV-1 capsid imposes rigidity and causes shifts in allosteric communication pathways connecting distant regions of the capsid protein. The authors of the Perspective anticipate that many other such exciting discoveries regarding virus capsid function and their use as drug targets lie just ahead on the horizon, and molecular dynamics simulations will drive these discoveries pending a series of notable advancements in computational methodology.

While waste recycling became popular in our daily life, living cells mastered waste recycling of their protein content since their very beginning. Recycling of unneeded protein molecules in cells is performed by a molecular machine called 26S proteasome, which cuts these proteins into smaller pieces and releases the pieces into the cell interior for reuse as building blocks for new protein. Proteins that need to be recycled are usually those that are misfolded. Proteins are recognized as such by the cells' so-called quality control system. This system labels misfolded proteins by a tag made of tetra-ubiquitin protein chains.

The 26S proteasome machine recognizes and binds to these tags via its subunit Rpn After Rpn10 binds to the tetra-ubiquitin tag and pulls the protein close, the 26S proteasome unwinds the tagged protein and cuts it into pieces. A recent study , based on molecular dynamics simulations with NAMD, sheds light onto how 26S proteasome and Rpn10 recognize the tetra-ubiquitin tag in three stages: In stage 1 of the recognition process conserved complementary electrostatic patterns of Rpn10 and ubiquitins guide protein association; stage 2 induces refolding of Rpn10 and tetra-ubiquitin tag; stage 3 facilitates formation of hydrophobic contacts between the tag and Rpn More information is available on our 26S proteasome website.

RNA molecules are continuously synthesized in living cells as carriers of biological information written in the sequence of basic RNA units, called nucleotides. To keep cells healthy, RNA molecules not longer needed or with errors have to be removed.

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A large barrel-like protein complex, the RNA exosome, is a molecular machine that degrades unneeded RNA molecules, pulling them inside its long internal channel and cutting them sequentially into single nucleotides. A new molecular dynamics study, employing NAMD, shows that a special active protein subunit of the exosome, called Rrp44, grips tightly the RNA molecule throughout its extended channel.

Rrp44 grips RNA molecules with five or more nucleotides in length while their ending nucleotides get sequentially cut, whereas shorter RNAs are only weakly bound and unlikely to be cut. The simulations reveal how the exosome can act both as a molecular motor that pulls RNA, without energy input other than the one released in nucleotide cleavage, as well as an enzyme that cuts RNA. More information is available on our RNA exosome website.

When experimental-computational biologists embarked on the great challenge of resolving the atomic level structure of the HIV virus capsid that contains the virus' deadly genetic cargo, they were advised by referees not to try as the capsid is too big, too irregular, and nobody would need the highly resolved structural information. Stubbornly, the researchers went ahead anyway and succeeded getting the atomic resolution structure, overcoming size and irregularity challenges see highlight Elusive HIV-1 Capsid.

But the question remained: Is the atomic level structure of the huge HIV capsid made of 1, proteins useless? The HIV capsid is a closed container made of protein pentamers and hexamers, with a surface of continuously changing curvature. Two recent experimental-computational studies demonstrate now that the capsid structure is far from useless, in fact, it is a great treasure. The first study was published last year and showed that the human protein, Cyclophilin-A CypA , involved in several diseases, interacts with the HIV capsid and affects the capsid's dynamic properties see highlight HIV, Cells and Deception.

In a second, recent study , guided by cryo-EM measurements and benefiting from large-scale molecular dynamics simulations with NAMD , researchers could resolve with new accuracy the binding of hundreds of CypA proteins on the capsid's surface. They found that CypA binds along high curvature lines of the capsid, which enhances stiffness and stability of the capsid, even though only about half of the capsid is actually covered by CypA.

The limited levels of CypA stabilize and protect the viral capsid as it moves through the infected cell towards the cell's nuclear pore where nuclear proteins additionally bind to the capsid at places not covered by CypA and promote there uncoating and release of the capsid cargo into the nucleus.

More information is available on our retrovirus website and in a news release. Motile bacteria position themselves within their habitats optimally, seeking proximity to favorable growth conditions while avoiding unfavorable ones. Cues used for this placement come in the form of small chemicals, so-called attractors and repellants, as well as physical factors such as favorable visible light and unfavorable UV radiation.

To balance such a broad range of factors, bacteria monitor their environments and respond by way of a fundamental sensory capability known as chemotaxis. Chemotactic responses in bacteria involve large complexes of sensory proteins, known as chemosensory arrays, that process the information obtained from the bacteria's habitat to determine its swimming pattern.

In this sense, the chemosensory array functions as a bacterial brain, transforming sensory input into motile output. Despite great strides in the understanding of how the chemosensory array's constituent proteins fit and work together, a high-resolution description of the kind needed to explore in detail the molecular mechanisms underlying sensory signal transduction within the array has remained elusive. A new study , utilizing cryo-electron microscopy and molecular dynamics simulations with NAMD , reports the highest resolution images yet of the bacterial brain's molecular anatomy.

Using computational techniques, structural data from X-ray crystallography and electron microscopy are compared to derive an atomically resolved model of the chemosensory array's extended molecular structure that involves millions of atoms. Subsequent simulations of the model revealed a novel conformational change in a key sensory protein, that is interpreted as a key signaling event in the translation of chemosensory information into swimming pattern. More details on this work can be found in a recent news release as well as on our bacterial chemotaxis website. DNA sequencing is achieved by following a strand of DNA at a speed that permits recognition of the DNA bases in their actual order, thousands of bases or more for each pass.

Nanotechnology can assist in the task, in principle, by furnishing sensors that can resolve single DNA bases and nano-mechanical actuators that pull the DNA in a controlled fashion passing through the sensor. Instead of building and testing actual sensors and actuators it is cheaper and faster to simulate them. Nanoengineers have indeed succeeded with such simulations over the last decade focussing on silicon technology see October highlight: Transistor Meets DNA. Now the engineers have moved with their simulations to graphene technology that promises much better resolving power as sensors are thinner and as signals can be detected electronically in graphene December and November highlights.

The main unsolved problem is the mechanical actuator: how can one control movement of DNA through a graphene sensor such that measured signals become less noisy and bases can be recognized? A recent study , based on molecular dynamics simulations with NAMD and quantum electronics calculations of graphene, suggests use of an actuator that simultaneously stretches the DNA and pulls it through the sensor. Read more on our graphene nanopore website. For centuries, millions of people around the globe have been troubled with a movement disorder that usually starts with a tremor in one hand.

The disorder, later known as Parkinson's disease, affects commonly older individuals and disrupts patient's movement, sleep and speech from the brain. There is currently no cure for the disease. Extensive studies have been carried out, yet the function of the protein remains a mystery. It is amazing that aggregation of such small proteins eventually leads to neuronal cell death and generates tremendous difficulties in peoples' life.

The discoveries, made possible through the software NAMD and VMD , are expected to shed light on the mechanism underlying Parkinson's disease and to inspire the design of drugs. The ribosome is the ubiquitous machine in all living cells responsible for translating the cell's genes into functional proteins. The majority of antibiotic drugs target the ribosomes of bacterial cells while leaving human ribosomes unharmed. An example are the most widely-prescribed antibiotics, erythromycin and telithromycin.

They kill bacteria by changing the properties of bacterial ribosomes and, thereby, disturb the bacterial protein production see the Oct highlight Antibiotic Action on the Ribosome. However, modern bacteria fight antibiotic drugs; exposing them to a specific kind of antibiotic drug for too long will trigger the expression of drug-resistance genes, which protect the bacteria, eventually making the drug useless. Due to historical overuse of antibiotic drugs, clinic antibiotic drugs have experienced today serious drug-resistance problems.

In a joint effort of computational and biomedical investigations, reported recently , molecular dynamics simulations with NAMD and systematic mutation experiments showed that the above antibiotics interact in a bacterial ribosome with a drug resistance gene - coded nascent protein and make it stall translation; however, engineered simple mutations in the bacterial gene can abolish stalling and, thereby, prevent the effect of drug resistance genes.

The research suggests that engineered mutations might be a strategy to prevent antibiotic resistance. Read more on our Ribosome website. When human immundeficiency virus HIV infects a human cell, it releases into the interior of the cell its capsid made of about 1, identical so-called CA proteins , a closed, stable container that protects the viral genetic material see also June highlight Elusive HIV-1 Capsid and August highlight Anatomy of a Dormant Killer.

The human-cell protein Cyclophilin A CypA is thereby exploited to act against the cell's well being and to assist the HIV infection by getting the capsid to access the cell nucleus; this results in a delicate choreography accomplished by escaping anti-viral proteins in the cell and deceiving transport proteins at the nucleus, all of which contain a CypA domain that interacts directly with the capsid.

Despite the availability of the crystal structure of the complex of CypA and CA proteins determined nearly 20 years ago, the mechanism by which CypA assists the capsid has been unclear due to the lack of information on CypA in complex with not one CA protein, but the entire capsid.

In collaboration with experimental groups, computational biologist have shown in a recent report that the effects of CypA on the capsid are not only structural, but also dynamical. Thus, new therapeutic strategies may be envisioned through modulation of the dynamics of the capsid by small-molecule drug compounds that inhibit the binding of CypA to the capsid. More information is available on our retrovirus website and in a YouTube video. The group has just completed its 40th hands-on computational biophysics training workshop see complete list , having now taught over 1, participants in intense, face-to-face, practical training sessions in small groups, typically of 30 students.

Participants are faculty, postdocs, industry professionals, and graduate students. The training material, in the form of very extensive tutorials, is freely available on the TCBG tutorial website. For more information, see the TCBG training website. After a retrovirus hijacks a cell, the infected cell produces multiple copies of the virus which are then released into the host's bloodstream.

These newly released viruses must mature before they can infect other cells. A strategy for preventing virus spread is therefore, to lock the viral particles in their immature, non-infectious state. However, to render the immature virus an attractive target for structure-based drug development one needs to know its chemical structure. As reported recently , a team of computational and experimental researchers have provided an atomic structure of the immature retroviral lattice for the Rous Sarcoma Virus.

The multi-domain RSV model was derived through a combination of state-of-the-art modeling techniques, including, cryo-EM-guided homology modeling, large-scale molecular dynamics simulations using enhanced sampling capabilities available in NAMD , together with experimental measurements such as X-ray crystallography and a wealth of biochemical data.

Particularly, the model reveals novel features of the packing and dynamics of the immature capsid protein with implications for the maturation process and confirms the stabilizing roles of the so-called upstream and downstream domains of the immature RSV. More information is available on our retrovirus website , and in a highlight video. Synthesis and placement of new proteins in a living cell poses a challenge for the cellular machinery, in particular in case of so-called membrane proteins.

Starting with nothing more than a sequence of DNA, the cell has to translate the genetic code, stitch together the constituent amino acids, and then place the newly made protein where its function is needed, namely the cell membrane. To meet the challenge the cell employs a molecular machine for the synthesis of proteins, the ribosome see the Dec.

Depending on the complexity of the membrane protein insertion, different protein systems are used for the translocation, in most cases the systems involving complexes of several, even many, proteins. Now however, the structure and function of the simplest translocating protein system has been solved, which actually is made of only a single protein, called YidC.

Despite its simplicity, structure determination of YidC was difficult, taking three decades. Successful structure determination was recently reported here , and involved the combination of cryo-electron microscopy, mutational experiments and computer simulations, the latter using NAMD , VMD and MDFF. The structure that was discovered shows a distinctive arrangement of five trans-membrane helices and reveals how a single copy of YidC interacts with the ribosome at the ribosomal tunnel exit and identifies a site for membrane protein insertion at the YidC protein-membrane lipid interface.

The quality of this atomic model is validated by its close agreement with a recently published crystal structure of E. Coli YidC here. More on our protein translocation website. Many processes in living cells require molecular motors.

Examples are transport of cargo within a cell, degrading misfolded proteins, and controlling gene expression. In the latter case acts a motor, called Rho, that moves along messenger RNA. The energy of the cell's motors stems from molecules of ATP that are converted to ADP, release thereby energy and drive motor action. How exactly this happens remained largely a mystery, despite decades of study and despite the availability of detailed molecular structures of the motors.

While molecular dynamics simulation, in principle, is well suited to explain Rho's motor action, the problem was that the action takes about a millisecond which is a time period beyond such simulations' reach. Employing new sampling methods, a recent publication , reported in new, complete and fascinating detail how Rho works. The simulations permitted literally to look under the hood of Rho's engine and see how it pulls itself along RNA and coordinates a cyclic and repeated motor action. It turned out that Rho, a ring of six identical protein subunits, engages in an ATP-to-ADP conversion-induced periodic motion of the subunits that pushes RNA electrostatically through the ring center.

A completely surprising finding was the existence of coordination switches that make each ATP-to-ADP conversion lead to exactly one forward step along the RNA and keep the six subunits strictly synchronized, turning a randomly moving protein system into a well-behaved engine. More on our molecular motor website. Long-range electrostatic interactions control macromolecular processes within living cells as prominent charges appear everywhere, such as in DNA or RNA, in membrane lipid head groups, and in ion channels.

Reliable and efficient description of electrostatic interactions is crucial in molecular dynamics simulations of such processes. Recently a new mathematical approach for calculating electrostatic interactions, known as multilevel summation method MSM , has been developed and programmed into NAMD 2. Compared to the earlier decades-long approach, the particle-mesh Ewald PME method, MSM provides more flexibility as it permits non-periodic simulations like ones with asymmetric charge distributions across a membrane or of a water droplet with a protein folding inside.

Furthermore, MSM is ideally suited for modern parallel computers, running, for example, simulations of large virus particles. More information here. Most living cells acquire their energy through photosynthesis or respiration, both of which convert input energy sun light or food, respectively through coupled electron and proton transfer processes. A key role is played here by a protein, called the bc 1 complex , that intermediately stores energy through the reaction of molecules of quinol into molecules of quinones, utilizing energy released to pump protons across an intracellular membrane.

This reaction is initiated in the bc 1 complex at the site of binding of the quinol molecule, but critical details about the physical mechanism leading to coupled electron-proton transfer are still unknown.

Modeling Solvent Environments - Applications To Simulations Of Biomolecules Hardcover

A recent study , based on molecular modeling with NAMD and quantum chemistry calculations, investigated possible reaction mechanisms in case of the bc 1 complex from the bacterium Rhodobacter capsulatus. The calculations suggest a novel configuration of amino acid residues responsible for quinol binding in the bc 1 complex, and support a mechanism for coupled proton-electron transfer from quinol to iron-sulfur cluster.

The study opens the door for a complete simulation description of the crucial role of the bc 1 complex in bioenergetics. The 1. For more insight, VMD 1. For more beauty, VMD 1. Such high quality graphics was previously available only on the most advanced computers, through powerful GPU-accelerated interactive ray tracing.

Interactive ray tracing makes the task of getting a molecular image "just right" much easier than ever before; it also enables rendering of spectacular movies, turning scientists into great film directors. See the light harvesting movie produced with VMD 1.

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Bacteria can make a living from a very wide range of food sources. This ability makes them, for example, essential symbionts in animal digestive tracts where they assist their hosts in breaking cellulose fibers up into compounds degradable by the animal metabolism. Today, human gut bacteria, part of the human microbiome, are one of the hottest research topics in medicine. Gut bacteria face a particularly tough job in the rumen of the cow where they digest hardy cellulose fibers of grasses.

Key to the job, taking place in a constantly moving fluid, are molecular tentacles, so-called cellulosomes, on the surface of the symbiotic bacteria. The cellulosomes develop a tight grasp on and then effective cleavage of cellulose. In a joint experimental-computational study researchers have investigated how in case of the bacterium Ruminococcus flavefaciens cellulosomes are built in a modular way, with molecular modules easily binding and unbinding during cellulosome construction, but sticking extremely strongly together during cellulosome digestive activity.

As reported recently , single molecule force microscopy and molecular dynamics simulations using NAMD could show that under strain the adhesive bonds between cellulosome modules become stronger than seen in any other biomolecular system, in fact, become nearly as tight as strong chemical bonds. While the experimental data revealed bond strength and other characteristics, simulations reproducing the observed data provided a detailed view of the adhesive bond at atomic resolution, thereby revealing the physical mechanism underlying the uniquely adhesive property of cellulosomes.

Gut bacteria and cellulosomes can be employed in 2nd generation biofuel generation see highlight Waste into Fuel. More on gut bacteria and cellulosomes on our biofuels website. A single such simulation of a hundred million atoms or more can utilize the tens of thousands of processors of petascale supercomputers thanks to recent advances in computational methodology reported here. Equally if not more significant, however, are advances in NAMD's implementation of multiple copy algorithms for enhanced sampling of smaller molecular systems as reported here. These algorithms have already allowed researchers studying the molecular machinery of living cells to reveal for the first time with NAMD mechanisms operating on timescales of milliseconds or longer, including the rotary action of the ubiquitous energy conversion complex ATP synthase and the inward to outward opening transition of the membrane transporter protein GlpT, shown in the accompanying animation.

Neurons in the brain form a closely knit communication network with other neurons. Each neuron sends messages through up to thousands of cell-cell communication channels, so-called synapses. To avoid communication chaos, the messages of each neuron are chemically encoded as if neurons speak English to some neurons and French to others. The neurons employ an extremely efficient encoding system, packaging chemical message molecules, so-called neurotransmitters, in spherical vesicles encapsulated by a lipid membrane just like the whole neuron is encapsulated by a membrane.

The vesicles aggregate near the presynaptic site of the membrane, ready to release their neurotransmitters into the space between neurons at the synapse, the so-called synaptic cleft. When a sender neuron becomes electrically active, as it wants to "speak", the electrical activity releases Calcium ions at the pre-synaptic cell that trigger merging fusion of vesicles with the sender neuron's membrane.

At this point the neurotransmitter molecules flow into the synaptic cleft. The receiver neuron "hears" the signal by receiving the neurotransmitter molecules on receptors in the postsynaptic membrane, inducing as a result an electrical signal in the receiver neuron. The release involves a group of proteins that make vesicles ready for the release and proteins that execute the Calcium-triggered step, among the latter synaptotagmin I.

As reported recently , researchers have proposed with the help of computer simulations using NAMD how synaptotagmin I acts. The finding, if true, will be a dramatic example for the role of computing in biology where the computer often complements observation studying, as in the present case, biomolecules in situ, namely their natural environment, rather than in vitro, namely in an artificial environment. Please read more on our neuron transmission website. Who needs a supercomputer to do molecular dynamics? Integrated into "Molecules" is the molecular dynamics code NAMD , which makes it possible to run real-time interactive simulations of the molecules in the book.

You can pull, stretch, and twist hundreds of different molecules, or even tie them in knots! By playing with the interactive molecular dynamics simulations , readers can get an intuitive feel for the properties of molecules - not to mention, they are just plain fun to play with. You can see the app for yourself in the iTunes App Store , read more about the creation of the app on Theodore Gray's blog , and see a screencast of honorary group member Sebastian pictured here playing with NAMD through the app on the atom molecule maitotoxin.

Threading DNA through a nanometer-size pore, so called nanopores, drilled into an ultrathin graphene membrane is a promising approach to build nanobiosensors for sequencing the human genome. Graphene nanopores can detect translocating DNA by recording concomitant flow of charged ions through the pore see December highlight. As reported in the December highlight, graphene, which is an electrical conductor, offers a new way of sensing DNA molecules by monitoring sheet currents along the graphene membrane.

DNA is a highly extensible molecule and upon mechanical manipulation can change its structure from a canonical helical conformation to a linear zipper-like conformation. A new study , which combines classical molecular dynamics simulations using NAMD with quantum mechanical simulations, suggests that sheet currents, in graphene membranes, can be used to detect conformation and sequence of a DNA molecule passing through the nanopore.

This new research will guide the development of graphene-based nanosensors for DNA detection. More information can be found on our graphene nanopore website. The ribosome, one of the ubiquitous molecular machines in living cells, is responsible for the critical task of translating the genetic code into functional proteins See also Managing the Protein Assembly Line.

The antibiotic action of macrolide drugs has been known for over 50 years, however, the molecular mechanisms underlying the effects of these drugs are still unknown. It was previously believed that the antibiotic action by macrolide drugs has to be assisted by the presence of a nascent protein inside the ribosome.

However, in a recent study , computational investigations jointly with biochemical experiments have revealed that the macrolide drugs can take an antibiotic action by altering the structure of the bacterial ribosome before translation of nascent protein really begins. Please see more highlights on translational control of the ribosome: Born to Control , Shutting Down the Protein Factory.

Biofuels are a well-known alternative to the largely used fossil-derived fuels, however the competition with food production is an ethical dilemma. Fortunately a solution is offered by second-generation biofuels, which can be produced from agricultural waste, or more specifically, from plant cell wall polysaccharides. Using the strategy of microorganisms, several enzymes are employed in the production of this advanced biofuel.

However the biofuel industry faces problems such as the loss of efficiency of the enzymes that arises over time due to intermittent high concentration of non-suitable substrates. Simulations can guide biochemical experiments aimed at investigating the mechanism that makes the enzymes vulnerable to such substrates, helping the development of more efficient and, thereby, less costly enzymes. A recent study , based on molecular modeling with NAMD , reported that reduction of efficiency in an important enzyme, know as Man5B, is associated with a loss of the enzyme's flexibility.

Molecular dynamis simulations showed that a poor substrate slows down a crucial opening and closing movement of the enzyme's catalytic cleft while a good substrate keeps the movement almost intact.


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The insight is of crucial importance since it suggests mutations to enzymes presently employed in second-generation biofuel production that need to be replaced less often and, thereby, rendering the production more cost-effective. Read more on our biofuels website. For many, the word 'X-ray' conjures up the images of white bones on black backgrounds hanging on the wall of a doctor's office. However, X-rays have played another important role for the past years through their use in the determination of chemical structures at atomic level detail, starting with the first ever structure of table salt in Since then, the diffraction properties of X-rays, when shone on a crystal, have been used to solve increasingly large and complex structures including those of biological macromolecules found inside living cells.

X-ray crystallography has become the most versatile and dominant technique for determining atomic structures of biomolecules, but despite its strengths, X-ray crystallography struggles in the case of large or flexible structures as well as in the case of membrane proteins, either of which diffract only at low resolutions. Because solving structures from low-resolution data is a difficult, time-consuming process, such data sets are often discarded. The method has been successfully applied to experimental data as described in a recent article where xMDFF refinement is explained in detail and its use is demonstrated.

Together with electrophysiology experiments, xMDFF was also used to validate the first all-atom structure of the voltage sensing protein Ci-VSP, as also recently reported. More on our MDFF website. These domains bind to parts of gene-silencing RNA that happens to form double strands, similar but not identical to the double strands formed by DNA and discovered long ago by Watson and Crick.

The simulations revealed that dsRBDs and double stranded RNA fit together ideally like matching pieces of a puzzle, with mutually compatible shapes and electrostatic patterns. On the other hand, dsRBDs and double stranded DNA or hybrid double strands have poor fits due to changed and insufficiently flexible double strand forms.

More here. Atomic force microscopy AFM gives us a low-resolution glimpse of life at the nanometer scale. Now scientists can bring microscopy images to life by combining the microscopy data with atomic-detail structures to re-create the imaged system on the computer. As recently reported , Center scientists constructed an atomic-resolution model of a photosynthetic membrane based on AFM data showing the locations of the many light-harvesting proteins that inhabit the membrane.

After using NAMD on petascale computers, like Blue Waters and Titan, to relax the million atom membrane, Center scientists used the model to study the migration of energy among the light-harvesting complexes, as well as the mobility of quinone molecules in the membrane. Read more on our website. The Golgi apparatus found in so-called eukaryotic cells acts like Amazon. However, in comparison to Amazon. The various lipids form membranes in the shape of vesicles. Depending on lipid type specific goods are packaged inside the vesicles, specific locations in the cell receive the packages, content is emptied there and packages are retrieved.

To achieve the series of steps just outlined, lipids as the main actors need to be coordinated.

One way is to recognize lipids forming vesicle membranes and to modify them to be readied for a subsequent step, for example going from release step to retrieval step. For this purpose eukaryotic cells engage a special class of proteins, named kinases, that can recognize membrane lipids and phosphorylate them, adding a so-called phosphate group. As reported recently , a team of experimental and computational scientists determined the atomic structure of a key member in the kinase family, phosphatidylinositol 4-kinase PI4K. The scientists discovered not only the structure, but also how PI4K captures and phosphorylates a particular type of lipid molecule, thereby changing a vesicular membrane and turning on the next step in the cellular package delivery system.

The discoveries, made possible through the software NAMD and VMD , are expected to have an impact on the design of novel drugs that suppress cancer cell growth. More on our kinase website. While pressure can help in cooking your favorite meat for dinner, pressure is also helping scientists to study how proteins, a key ingredient in any meal, loose and regain their proper shape. Proteins are key building blocks for any life form on earth, making the many machines that drive living cells.