Motor proteins transport cargos from one place in living cells to another, for example transport cell components along the long axons of nerve cells. A motor protein, such as myosin VI, has to "walk" or "run" along the cellular highway of actin filaments to perform the transport. In the case of myosin VI, snapshots from crystallography revealed that the protein's "legs" are too short to explain the step size taken. Computational and experimental biophysicists have now solved the mystery of how myosin VI dimers realize their large step size despite their short legs.
The investigation, based on the program NAMD and reported recently, demonstrates that the answer lies in the flexibility of the legs. Myosin VI is able to triple the length of each leg, made of a short bundle of up-down-up connected alpha-helices, by extending the bundle to a stretched-out down-down-down geometry of segments, like turning a letter z into a a single long line. In the telescoping process, myosin VI also gets help from its well-known binding partners, namely calmodulins. The calmodulins direct the telescoping of the protein legs as well as strengthen the extended legs. Together with an earlier study of the "neck" region of the molecule (see December 2010 highlight on Opposites Attract in a Motor Protein), the scientists have established how walking myosin VI achieves its wide stride. More information can be found on our motor protein website.
A cell that is alive can be recognized typically under a microscope through cell motion, streaming of inner cell fluids, and many other mechanical cell activities. These activities are the result of mechanical forces that arise in the cell, but even though the effect of the forces on cells are tremendous, the magnitude of the forces when measured by physical instruments, are extremely small, 1/1000000000000 of the force felt when lifting a Kilogramm. Sensing such small force requires extremely high precision in research techniques, and, for more than a decade, computational biologists, using NAMD, have exploited the all-atom resolution of molecular dynamics modeling to explain very successfully the molecular level effect of small forces in cells (for example, see our previous highlights on muscle protein, blood clot protein, and other successful applications). But simulations, too, are challenged by the small magnitude of cellular forces, mainly because precise simulation requires extremely extensive simulations, that cover a duration as close as possible to the biological time scale. Advances in computational biology have now permitted in the case of a the muscle protein titin a simulation of unprecedented accuracy that resolved clearly the relationship between molecular structure of titin and its ability to sustain the forces that arise in muscle function. For this purpose a key element of titin was stretched at a velocity slow enough that hydrodynamic drag, that came about as an unwanted byproduct of earlier simulations, was negligible compared to titin's intrinsic force bearing properties. The new simulations opened an unveiled view on muscle elasticity. More information can be found on our titin website, and in a recent review .
Motor proteins are fascinating cellular machines that convert chemical energy into mechanical work. They are employed in a wide range of cellular functions like muscular contraction, transportation of proteins and vesicles, and cell motility. Myosin VI is an example of a motor protein. It "walks" along actin filaments (kind of like cellular highways), performing tasks such as delivering materials across the cell. Primarily, myosin VI functions as a dimer (i.e., two myosin VI proteins are associated and form a functional complex), but the structure of the myosin VI dimer, particularly how a myosin VI associates with another one, is still debated. Teaming up with experimentalists, computational biologists investigated how two myosin VI assemble and pull their cargo together. The investigation, reported recently, focused on a segment of myosin VI that forms a long, rigid alpha-helix that is notably decorated with a distinct rings of positively and negatively charged amino acids. Carrying out single-molecule experiments along with molecular dynamics simulations using NAMD, it was found out that two myosin VI proteins attract each other electrostatically through the charge-ring proteins, shifting them such that the oppositely charged amino acids from different helices face each other. More information can be found on our motor protein website.
The process of photosynthesis fuels life on Earth. Its first step is capturing the energy in sunlight. Light-capturing proteins in photosynthetic organisms are often seen closely crowded together in the cellular membrane, forming hundred nanometer-sized patches. Such "photosynthetic membranes" can be flat or spherical, depending on bacterial species (see the October 2007 highlight on Life's Solar Battery, the August 2010 highlight on Bacterial Solar Energy Engineering, and a recent review); in case of a certain mutant bacterium the membrane forms the cylindrical surface of a rod. This membrane is actually an ideal case for scientific investigation, since it contains only one type of protein complex organized in an orderly fashion, such that placement of all proteins is known with atomic precision. As reported recently, researchers have used the cylindrical photosynthetic membrane as a model system to elucidate in great detail how light is captured, and how the light energy is passed around the light-capturing proteins until it is utilized to charge the membrane through electron transfer. The theory of these quantum mechanical processes has been described before (see the April 2010 highlight on Light Capture). More information can be found on our photosynthetic core complex website.
A smart strategy usually involves a plan B. As it turns out, the muscle proteins in our bodies responsible for the physical motions like running or the beating of our hearts, also rely in their function on having a plan B strategy. When contracting and extending, muscle fibers generate tremendous forces that need to be buffered to protect muscle from damage. This role falls to the muscle protein titin, which is composed of a chain of linked domains, making it a molecular rubber band. When a small force is applied, titin employs its plan A and stretches apart without unraveling its individual domains (like what the movie on the side shows). When a stronger force is applied, plan B kicks in and further elasticity is generated by the unwinding of the protein domains one at a time. By practicing two modes of response to different levels of forces, titin provides the elasticity that muscle needs at a minimal structural cost. A recent computational-theoretical investigation has provided a molecular view on how titin's two plans work, the study featured in a journal cover. The needed simulations were performed using NAMD. Principles described in this study can also be found in other mechanical proteins, recently reviewed here. More on our titin IG6 website.
Bacteria contain the simplest photosynthetic machineries found in nature. Higher organisms like algae and plants practice photosynthesis in a more elaborate but principally similar manner as bacteria. But even for its simplicity, the bacterial photosynthetic unit is not without its unsolved mysteries. Take, for example, the crucial photosynthetic core complex, which performs light absorption and the initial processing of the light energy. In certain bacterial species, the core complex contains two copies of an additional small protein (made of about 80 amino acids) called PufX, whose role in photosynthesis is still a puzzle, and its location within the core complex is yet to be pinpointed. Numerous imaging studies have been published, yielding two opinions on what the role of PufX is and where exactly it resides. One opinion assigns the protein the role of gate keeper, the other the role of coordinator. Recently, a computational investigation was carried out that much supports the second role. Since PufX comes as a pair, two copies of PufX were placed side-by-side in a biological membrane and they were seen to adhere to each other strongly, but assume with their cylindrical (helical) shape an angle of 38 degrees. This geometry is perfectly suited for PufX to join the two parts of the symmetrical core complex together in the middle and to impose on the parts the tilt that was actually observed in the imaging studies. The needed simulations were done with NAMD. More details can be found on our photosynthetic core complex website.
Proteins are the workers in cells; they carry out designated cellular functions tirelessly throughout their lifetimes. Some proteins can even hold two different jobs. One example of a dual-duty protein is the bacterial photosynthetic core complex. The photosyntehtic core complex performs the first steps of photosynthesis: absorption of sunlight and processing of light energy. Besides providing solar power, the core complex acts as an architect of the cell by shaping membranes in the interior of photosynthetic bacteria. Combining computational modeling and electron microscopy data using the Molecular Dynamics Flexible Fitting method, computational biologists have recently reported studies of both functions of the core complex, namely, the light-absorbing features and the membrane-sculpting properties. More details can be found on our photosynthetic chromatophore website.
Chromatophores are the photosynthetic machineries of bacteria. Each chromatophore contains, embedded in a membrane, all the photosynthetic proteins needed to absorb sunlight and turn it into chemical fuel. Chromatophores come in different shapes: while some chromatophores are spherical, others are flat or tubular. It has puzzled scientists how all these different geometries arise, and a hypothesis has developed that it is the photosynthetic proteins that render the shape of chromatophore membrane. In a study reported recently, computational biologists using NAMD took an atomistic look at how the chromatophore proteins bend the membrane. Simulations showed that the most numerous photosynthetic proteins dome the membrane, building arched membrane patches that can then be assembled into a spherical chromatophore. These simulations demonstrated that photosynthetic proteins construct their individual membrane environment, and when many of such proteins come together in the bacterial membrane, they can build functional cellular units with unique geometries. For more details, please see our chromatophore website.
Muscle fibers, in contracting and extending, generate tremendous force that needs to be buffered to protect muscle from damage. This role falls to the protein titin, with about 27,000 amino acids the longest protein in human cells. Titin functions as a molecular rubber band, but unlike uniform rubber bands, titin is made from over 300 different protein domains strung into a chain. While experiments have found that the individual domains of titin feature remarkable resilience against mechanical stretching, little is known about the elasticity of the overall titin chain. Crystallographers teamed up with computational biologists to investigate this elasticity, focusing on two adjacent titin domains. Molecular dynamics simulations using NAMD suggest, as reported recently, that the overall elasticity of the titin chain stems in part from a zigzag, i.e., accordion-like, motion: as titin is contracted and extended, energy is stored and released in the angular tilt of adjacent domains. More on this investigation can be found here.