Molecular motors are efficient nanoscale machines destined to make any human designed engine look clumsy. F1-ATPase is such a machine - so powerful that a spoonful of it could produce as much torque as your car's engine. As part of the enzyme ATP synthase, the protein can work as an engine but also operate in reverse as a generator. In the latter mode it is responsible for the synthesis of the energy-rich molecule ATP that serves as fuel driving many processes in biological cells. It can also convert the energy stored in ATP into mechanical rotation. Our studies suggests that the analogy to a car's engine goes even further! A quantum chemical description of the reaction of ATP combined with a simulation of the protein revealed that an amino acid side group of the protein, called the "arginine finger", controls the progression of the catalytic event, much like a spark plug controls the combustion process in a car engine. The very extensive simulation made use of a powerful computer, the Jonas Cluster at the Pittsburgh Supercomputing Center. The investigation is yet another example for the important role of computational biology unraveling the secret behind the function of the machinery of living cells.

Light harvesting complexes provide fascinating challenges to biophysicists. With the availability of atomic structures for protein-pigment complexes such as photosystem I, it is possible to form a comprehensive picture of the light absorption and excitation migration processes based on an atomic level quantum mechanical description. This kind of structural analysis not only forms a rigorous test for our understanding of the physics of these mechanisms through a comparison to spectroscopy and kinetics experiments, but it also provides a framework within which the organizational principles for multi-component pigment-protein assemblies can be investigated.

In light-harvesting complexes, carotenoids act as light-absorbers in the blue-green region of the spectrum. Absorption of a photon is followed by rapid singlet excitation energy transfer to bacteriochlorophyll (BChl). In addition to their light-harvesting role, carotenoids photoprotect antenna complexes, i.e., they prevent the formation of photo-oxidizing singlet oxygen by quenching BChl triplet states through triplet excitation transfer. Light-harvesting and photoprotection by carotenoids is studied in Theoretical Biophysics Group in two proteins, the Light-Harvesting Complex II of Purple Bacteria, and the Peridinin-Chlorophyll-Protein of Dinoflagellates.

Plants and other photosynthetic organisms convert sunlight into various forms of metabolic energy. To expose themselves optimally to the sun while at the same time avoiding damaging overexposure to light, these organisms employ molecular photosensing systems that control, for example, the orientation of their leaves. Common photosensing systems include photoreceptors of the so-called phot family that are sensitive to blue light and contain Light, Oxygen, and Voltage (LOV) sensitive protein domains as photoactive elements. Light absorbed by a flavin molecule leads to bond formation with the protein (LOV domain), thereby, initiating signaling until the flavin-protein bond breaks spontaneously. Our study of the photosensing events in the LOV domain of the algae C. reinhardtii employs computer simulations that combined quantum mechanical and classical simulation methods to study photoexcitation and subsequent processes. It emerged that formation of the flavin-protein bond is initiated by a unique light-driven transfer of a hydrogen atom between the LOV domain and the flavin molecule.

The rhodopsin receptors reside in the cell membrane, and function as sensors of light. These proteins consist of an apoprotein (opsin) and a retinal chromophore covalently bound to the apoprotein by a protonated Schiff base linkage to a lysine residue. While the protonated form of retinal Schiff base absorbs at about 440 nm in organic solvents, its maximal absorption is drastically changed after binding to the apoprotein, an effect known as 'opsin shift'. A fundamental challenge in vision research has been the elucidation of the physical mechanisms by which the protein matrix adjusts the maximal absorption of the chromophore, using the molecule retinal to detect light at different wavelengths. The spectral tuning in two very homologous rhodopsins, sensory rhodopsin II and bacteriorhodopsin, is investigated by means of a combined ab initio quantum mechanical/molecular mechanical calculation.

The all-trans retinal protonated Schiff base (RSPB) is the chromophore of bacteriorhodopsin (bR), a transmembrane protein that acts as a light-driven proton pump in Halobacterium salinarium, converting light energy to a proton gradient. Upon absorption of light the chromophore undergoes a photoisomerization process (all-trans -> 13-cis) that eventually provides the driving force for the translocation of protons. This elementary photoisomerization process proceeds on multiple coupled potential energy surfaces and we have modeled it using a formally exact quantum-mechanical procedure: the full multiple spawning method. Currently, we are studying the first excited electronic state of the chromophore using an isolated retinal analog model and ab initio CASSCF methods. The characterization of the first excited state (minima and conical intersections associated with isomerization around different double bonds) will enable us to extend and improve the aforementioned quantum-mechanical studies of the photoreaction dynamics in the protein.

The five human senses are based on amazingly sensitive molecular processes: smell and taste are based on molecular recognition, hearing and touch on molecular mechanics, vision on molecular electronic excitation. Some animals have additional sensory capabilities; for example, some possess a magnetic sense used for orientation by means of the geomagnetic field. The magnetic sense has long been poorly understood since the underlying molecular process could not be identified, but recently some progress has been made. Surprisingly, animal vision has been implicated and evidence has been accumulated that animals can see the geomagnetic field. A long-hidden receptor in the eye, a protein aptly called cryptochrome, is likely involved. Unfortunately, cryptochrome exists only in minute amounts in animal eyes, e.g., those of migratory birds, so that only behavioral measurements on animals can be taken, but not physical measurements directly on cryptochromes. Fortunately, cryptochromes exist also in plants where they control hypocotyl growth inhibition in seedlings. Experimentalists have observed that cryptochrome-dependent responses in Arabidopsis thaliana seedlings are magnetic-field-dependent. Researchers have now also computationally demonstrated that light activation of plant cryptochrome is magnetic-field-dependent. A recent report showed that light excitation leads to cascading electron transfer in which electron spins are influenced by weak magnetic fields; the spin dynamics was found to influence the activation of cryptochrome. Arabidopsis thaliana cryptochrome can be produced in quantities large enough for physical measurements so that the door is now wide open for cracking the secret behind the long-mysterious magnetic sense of animals. More on our cryptochrome web site.

DNA with its famous double helix structure stores the genetic information of all life forms known. In order that this information is read, the double helix needs to be first unwound and separated into single helices or strands. This is achieved by cellular motor proteins called helicases that operate on already separated DNA strands. The helicases specialize in unwinding and separating the DNA double helix by scooting along one of DNA's single strands against the point where the two strands merge into the double helix; pushing against this point unwinds and separates the double helix further. The helicases are driven by energy stored in molecules of ATP which bind to the protein and get released in their so-called hydrolyzed, lower energy, form. Based on atomic resolution structures, researchers have studied now one of the smallest helicases known, PcrA, from the electronic to the functional level carrying out quantum mechanical/molecular mechanical simulations (as described in a first publication), as well as a combination of classical molecular dynamics simulation, using NAMD, and stochastic modeling calculations (described in a second publication). This resulted in an overall explanation of how ATP's hydrolysis powers helicase activity which has been reported in a third publication. The researchers discovered that PcrA moves with two "hands" along single stranded DNA; when ATP binds, one "hand" moves along the DNA; when ADP and Pi (the hydrolysis products of ATP) unbind, the other "hand" moves; through a molecular "trick" both "hands" move in the same direction. Amazingly, the hand movement arises mainly from an increase in random mobility of the hands. i.e., is not enforced. Physicists refer to the underlying mechanism as a ratchet mechanism that was indeed long suspected to drive molecular motors. Interestingly, the helicase motor is very closely related to a wide class of other biological motors, for example the FoF1-ATP synthase (see Mar 2004 and Nov 2004 highlights). For more information visit our helicase research website.

Photosynthetic units (PSUs) of living organisms are complex assemblies of several multi-protein aggregates. We constructed the structure of the PSU of purple bacteria. The components involved were the crystal structure of the bacterial photosynthetic reaction center surrounded by the model structure of the light-harvesting complex I and several structures of the light-harvesting complex II, solved in a collaborative project with X-ray crystallographers. The constructed structure is used to study the light energy transfer driving the bacterial photosynthesis.

The ability to sense light is crucial for both plants and animals; animals use their vision to navigate and interact with their surroundings, whereas plants grow toward light to optimize photosynthesis. One of the most important photosensors in plants relies on tiny molecular switches known as LOV domains. When light strikes a LOV domain, it causes the formation of a single chemical bond; the unique structure of the LOV domain converts this subtle change into a protein unfolding event that triggers signaling. The mechanism through which LOV domains amplify bond formation into large-scale molecular motion is of great interest both for designing light-activated proteins for synthetic biology applications, and as a model for understanding the harder-to-study molecular switches that govern most of the functions of living cells. As reported recently, researchers used a series of long-timescale molecular dynamics simulations to show the locations of molecular levers that allow light-induced bond formation to rearrange the entire structure of the LOV domain. The simulations highlighted two main paths of information flow from the heart of the photoreceptor to the surface of the protein, giving unprecedented insight into the function of this light-activated molecular switch. More information is available on the biological photoreceptors website.

Excitation transfer between pigment molecules, such as bacteriochorophylls (BChls), and between pigment-protein light harvesting complexes, such as light harvesting complex 2 (LH2), has been investigated for many years using many different theoretical descriptions. Typically these descriptions include a priori assumptions about the dynamics of the system. Such assumptions are often made due to incomplete knowledge to make the system numerically tractable so that further insight can be gained. In the theoretical models of excitation transfer, it is often assumed that one parameter is much larger than another, allowing the system to be treated perturbatively. These assumptions, however, should be physically reasonable and should be tested if possible.

Olfaction is the sense of smell. This sense is mediated by specialized sensory cells of the nasal cavity of vertebrates. Many vertebrates, including most mammals and reptiles, have two distinct olfactory systems—the main olfactory system, and the accessory olfactory system (used mainly to detect pheromones). For air-breathing animals, the main olfactory system detects volatile chemicals, and the accessory olfactory system detects fluid-phase chemicals. Olfaction, along with taste, is a form of chemoreception. The chemicals themselves that activate the olfactory system, in general at very low concentrations, are called odorants. Volatile small molecule odorants, non-volatile proteins, and non-volatile hydrocarbons may all produce olfactory sensations. Some animal species are able to smell carbon dioxide in minute concentrations.

Green sulphur bacteria harvest sunlight by absorbing solar energy in large pigment-containing vesicles known as a chlorosomes and transporting this energy to a reaction center for charge separation. Along the way, excitation absorbed by the chlorosome is passed through the Fenna-Matthews-Olson (FMO) complex to get to the reaction center complex. As this process occurs in a biological environment, there is a significant amount of thermal noise present. As excitation is passed between pigments, from the bacteriochlorophylls in the chlorosome to those in FMO and finally to those in the reaction center, it is constantly under the influence of thermal fluctuations. It is of importance then that FMO can efficiently conduct excitation energy, i.e., without much energy loss. One way to do this could be by exploiting quantum coherence to speed up energy transfer.

Photosynthesis, the main source of energy for all life, is performed by an intricate assembly of hundreds of proteins, which harvest, transfer, convert, and store solar energy. The simplest such light harvesting machine is the purple bacterial photosynthetic unit (PSU), which performs anoxygenic photosynthesis and is significantly simpler and evolutionarily more primitive than its counterpart found in plants. The bacterial PSU is organized in the form of a pseudo-spherical membrane domain of approximately 60 nm diameter called a chromatophore vesicle.

Quantum mechanics rules all natural processes, but is manifested most strongly when acting on the lightest particles, namely the well-known electrons. To study quantum effects physicists routinely resort to very low temperature, that of liquid helium. Amazingly, living systems seem to exploit quantum effects for their benefit, but do so at temperatures typical for life, namely around room temperature or warmer. A particularly important case is photosynthetic light harvesting where so-called quantum coherence plays a critical role when electrons in assemblies of chlorophylls become excited by sun light and the excitation energy is harvested by utilizing it to charge photosynthetic membranes. In order to understand how photosynthesis can exploit room temperature quantum effects one needs to know how the temperatures, which are much higher than those in the physics laboratories where liquid helium is employed for cooling, affect electron behavior. The knowledge can be gained by so-called dissipative quantum mechanical descriptions, but the needed computer calculations are extremely demanding. To address this demand, researchers have developed the software PHI that uses the power of parallel computers, as described here. PHI has already been used to understand how many chlorophyll molecules act together to absorb sunlight among themselves and let the excitation migrate between chlorophylls to so-called reaction centers where the excitation energy is converted into a membrane potential. The PHI software can be obtained from our web site. More information on PHI is available here.