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.

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.

Bacterial cells can swim and use for this purpose one or more flagella, whiplike appendages that exceed the length of the cell severalfold. The flagella are made of many thousand copies of a protein called flagellin, arranged in a helical fashion such that the flagella are hollow inside, forming a very long channel. When the flagella are rotated by the cell counter-clockwise, the cell swims straight; when they are rotated clockwise, the cell turns to a new direction. Through swimming and turning the cell searches its habitat for food and avoids trouble. But sometimes a flagellum breaks and needs to grow back. At this point starts an amazing process: the cell makes new flagellin and pumps the unfolded protein into the flagellar channel, extending its length. This is like squeezing toothpaste out of a tube, except in reverse, like pumping toothpaste into the tube at the toothpaste factory, and the tube is extremely long. Now researchers have described the process that makes flagella grow step-by-step through a combination of mathematics, physics, and molecular modeling using NAMD. As reported, the researchers reproduce the time course of growth as well as the length of the growth and also explain how friction of the protein paste is kept extremely low to make the flagella grow many times the length of the cell itself. More information here.

Like all organisms, bacteria have to eat. However, bringing nutrients in from the outside world is not an easy task for many bacteria that are surrounded by an extra membrane. The second membrane, called the outer membrane, offers additional protection but at a cost: no energy can be generated or stored at the outer fringes of the cell. So, to import large, rare nutrients that cannot cross by diffusion alone, bacteria have evolved a unique transport system which couples the inner, energy-generating membrane to the passive outer membrane, known as the TonB-dependent transport system. TonB, an inner membrane-associated protein, transfers energy across the periplasm to a variety of outer-membrane transporters. These transporters have a large, beta-barrel structure which is blocked in the middle by a plug called the 'luminal domain'. How TonB transfers energy to the transporter and causes the luminal domain to come out is still a mystery though. Now with the help of computer simulations using NAMD and a recent crystal structure of TonB coupled to BtuB, the transporter responsible for vitamin B12 transport, researchers have shown that TonB can mechanically activate the transporter by pulling on the luminal domain, causing it to leave the barrel. Using steered molecular dynamics, it was found that TonB stayed firmly attached to the luminal domain of BtuB, even though the contact between the two is limited to just a handful of residues. Furthermore, this pulling initiated unfolding of the luminal domain, opening a transport pathway for the substrate. These results, the subject of a recent publication and also highlighted in Science, demonstrate how a mechanical coupling can bridge the gap between the two membranes, thus enabling outer membrane transport.

The bacterial flagellum is a large biomolecular assembly used by many types of bacteria as a helical propeller for forward swimming and turning. The flagellum is remarkable in that its properties differ greatly depending on the direction in which it is rotated, allowing the bacterium to switch between swimming straight ("running") and turning ("tumbling"). The mechanics of the flagellum are of interest both to biologists and mechanical engineers. The molecular mechanisms of the transition in the flagellum between running and tumbling modes is unknown. Because of the flagellum's size (several micrometers in length) and composition (made up of 30,000 protein subunits) it presents a challenge to computational modeling. Researchers have now achieved an advance describing the flagellum in both its running and tumbling state. For this purpose, the researchers developed a computational model of the system that glosses over atomic level detail, but resolves the shapes of all proteins making up a bacterial flagellum, simulating a simplified version of the system using the program NAMD. The results, reported recently, showed that the flagellum's transition between swimming straight and tumbling is triggered by friction due to the water around the bacterium. More information on the flagellum project can be found here.

Escherichia coli are bacteria living in the intestines of mammals as part of their healthy gut flora, but also causing disease outside of the gut. The bacteria import from their environment nutriments, for example molecules of lactose, a sugar. For this purpose Escherichia coli employs in its cell membrane a protein channel, lactose permease, that translocates the sugar outside-in. This is the bacterium's "sweet tooth". To establish the unidirectional sugar transport, the bacterium utilizes an electrical potential maintained in the form of a trans-membrane proton gradient (more protons on the outer cellular than on the inner cellular side of the membrane). Protons, very small ions, that enter the channel from the outside one at a time, open the outer channel entrance. This permits access of lactose that gets bound inside the channel. Release of the proton to the cell interior closes the outer channel entrance and opens the inner channel entrance, such that the bound lactose can enter the cell. Despite extensive and elegant biochemical studies, the physical mechanism that couples unidirectional proton and sugar translocation is not yet known in detail. A crystallographic structure of lactose permease permitted now investigations into this mechanism by means of molecular dynamics simulations using NAMD. The simulations, reported in a recent publication, showed one step of the proton - sugar translocation, namely how binding and unbinding of the proton activates a spring-like bond, a so-called salt bridge, that closes and opens the inner channel exit. More information on the lactose permease project can be found here.