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.

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.

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.

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 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.

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.

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.

We study the suggestion that the geomagnetic field is detected by changes in the rates and yields of radical pair reactions. Assuming that photoreceptors involved in vision are involved in radical pair reactions, the magnetic field will result in a modulation of vision. The visual modulation patterns furnish animals with magnetic compass capabilities as illustrated in the figure.

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.