arXiv subjects

Klaus Schulten

Publications and source records attributed to Klaus Schulten.

13 recordsLinked to original sources

arXiv2014

Single Molecule FRET Reveals Pore Size and Opening Mechanism of MscL

The mechanosensitive channel of large conductance, which serves as a model system for mechanosensitive channels, has previously been crystallized in the closed form, but not in the open form. Ensemble measurements and electrophysiological sieving experiments show that the open-diameter of the channel pore is >25Å, but the exact size and whether the conformational change follows a helix-tilt or barrel-stave model are unclear. Here we report measurements of the distance changes on liposome-reconstituted MscL transmembrane α-helices, using a "virtual sorting" single-molecule fluorescence energy transfer. We observed directly that the channel opens via the helix-tilt model and the open pore reaches 2.8 nm in diameter. In addition, based on the measurements, we developed a molecular dynamics model of the channel structure in the open state which confirms our direct observations.

q-bio.BM↗

arXiv2011

Mechanism of magnetic field effect in cryptochrome

Creatures as varied as mammals, fish, insects, reptiles, and migratory birds have an intriguing `sixth' sense that allows them to distinguish north from south by using the Earth's intrinsic magnetic field. Yet despite decades of study, the physical basis of this magnetic sense remains elusive. A likely mechanism is furnished by magnetically sensitive radical pair reactions occurring in the retina, the light-sensitive part of the eyes. A photoreceptor, cryptochrome, has been suggested to endow birds with magnetoreceptive abilities as the protein has been shown to exhibit the biophysical properties required for an animal magnetoreceptor to operate properly. Here, we propose a concrete light-driven reaction cycle in cryptochrome that lets a magnetic field influence the signaling state of the photoreceptor. The reaction cycle ties together transient absorption and electron-spin-resonance observations with known facts on avian magnetoreception. Our analysis establishes the feasibility of cryptochrome to act as a geomagnetic compass in birds, gives insight into structural and dynamic design features required for optimal detection of the geomagnetic field direction, and suggests further theoretical and experimental studies.

physics.bio-ph↗

arXiv2005

The Dynamics of Image Processing by Feature Maps in the Primary Visual Cortex

The operational characteristics of a linear neural network image processing system based on the brain's vision system are investigated. The final stage of the network consists of edge detectors of various orienations arranged in a feature map, corresponding to the primary visual cortex, or V1. The lateral geniculate nucleus is modeled as a preprocessing stage. Excitatory forward and inhibitory backward connections exist between the LGN and V1. By a method of reconstructing the input images in terms of V1 activities, the simulations show that images can be faithfully represented in V1 by the proposed network. The signal-to-noise ratio of the image is improved by the representation, and compression ratios of well over two-hundred are possible. Lateral interacations between V1 neurons sharpen their orientational tuning. We further study the dynamics of the processing, showing that the rate of decrease of the error of the representation is maximized for the receptive fields used, and we develop a Fokker-Planck equation for a more detailed prediction of the error value vs. time. Finally, we show how the eigenvalues of the covariance matrix of the inputs can be employed to predict the rate of error decrease.

q-bio.NC↗

arXiv2005

Receptive Field and Feature Map Formation in the Primary Visual Cortex via Hebbian Learning with Inhibitory Feedback

A linear neural network is proposed for mamalian vision system in which backward connections from the primary visual cortex (V1) to the lateral geniculate nucleus play a key role. The backward connections control the flow of information from the LGN to V1 in such a way as to maximize the rate of transfer of information from the LGN to V1. The application of hebbian learning to the forward and backward connections causes the formation of receptive fields which are sensitive to edges, bars, and spatial frequencies of preferred orientations. Receptive field types in V1 are shown to depend on the density of the afferent connections in the LGN. Orientational preferences are organized in the primary visual cortex by the application of lateral interactions during the learning phase. Change in the size of the eye between the immature and mature animal is shown be an important factor in the development of V1 organization. The orgainization of the mature network is compared to that found in the macaque monkey by several analytical tests.

q-bio.NC↗

arXiv2004

Fluctuation-Driven Molecular Transport in an Asymmetric Membrane Channel

Channel proteins, that selectively conduct molecules across cell membranes, often exhibit an asymmetric structure. By means of a stochastic model, we argue that channel asymmetry in the presence of non-equilibrium fluctuations, fueled by the cell's metabolism as observed recently, can dramatically influence the transport through such channels by a ratchet-like mechanism. For an aquaglyceroporin that conducts water and glycerol we show that a previously determined asymmetric glycerol potential leads to enhanced inward transport of glycerol, but for unfavorably high glycerol concentrations also to enhanced outward transport that protects a cell against poisoning.

physics.bio-ph↗

arXiv2003

Modeling DNA loops using the theory of elasticity

A versatile approach to modeling the conformations and energetics of DNA loops is presented. The model is based on the classical theory of elasticity, modified to describe the intrinsic twist and curvature of DNA, the DNA bending anisotropy, and electrostatic properties. All the model parameters are considered to be functions of the loop arclength, so that the DNA sequence-specific properties can be modeled. The model is applied to the test case study of a DNA loop clamped by the lac repressor protein. Several topologically different conformations are predicted for various lengths of the loop. The dependence of the predicted conformations on the parameters of the problem is systematically investigated. Extensions of the presented model and the scope of the model's applicability, including multi-scale simulations of protein-DNA complexes and building all-atom structures on the basis of the model, are discussed.

physics.bio-ph↗

arXiv2002

Reaction Pathways Based on the Gradient of the Mean First-Passage Time

Finding representative reaction pathways is necessary for understanding mechanisms of molecular processes, but is considered to be extremely challenging. We propose a new method to construct reaction paths based on mean first-passage times. This approach incorporates information of all possible reaction events as well as the effect of temperature. The method is applied to exemplary reactions in a continuous and in a discrete setting. The suggested approach holds great promise for large reaction networks that are completely characterized by the method through a pathway graph.

physics.chem-ph↗

arXiv2002

Representative Pathways of Excitation Migration in Photosystem I

Photosystem I is a protein-pigment complex that performs photosynthesis in plants, green algae, and cyanobacteria. It contains an aggregate of chlorophylls that absorbs light and delivers the resulting electronic excitation to the special pair of chlorophylls where the excitation energy is used for producing charge separation across the cell membrane. The seemingly random arrangement of chlorophylls in photosystem I poses the question which pathways excitation migration follows towards the special pair after absorption of light at any of its chlorophylls. We employ a master equation to describe the process of excitation migration in photosystem I, and find representative paths of excitation migration based on the mean first-passage time from each chlorophyll to the special pair. The resulting paths, beginning at each of the chlorophylls and ending at the special pair, provide a complete yet distilled picture of the excitation migration towards the special pair.

physics.bio-ph↗

arXiv2002

Robustness and Optimality of Light Harvesting in Cyanobacterial Photosystem I

As most biological species, photosynthetic lifeforms have evolved to function optimally, despite thermal disorder and with fault tolerance. It remains a challenge to understand how this is achieved. To address this challenge the function of the protein-pigment complex photosystem I (PSI) of the cyanobacterium Synechococcus elongatus is investigated theoretically. The recently obtained high resolution structure of this complex exhibits an aggregate of 96 chlorophylls that are electronically coupled to function as a light-harvesting antenna complex. This paper constructs an effective Hamiltonian for the chlorophyll aggregate to describe excitation transfer dynamics and spectral properties of PSI. For this purpose, a new kinetic expansion method, the sojourn expansion, is introduced. Our study shows that at room temperature fluctuations of site energies have little effect on the calculated excitation lifetime and quantum yield, which compare favorably with experimental results. The efficiency of the system is found to be robust against `pruning' of individual chlorophylls. An optimality of the arrangement of chlorophylls is identified through the quantum yield in comparison with an ensemble of randomly oriented chlorophylls, though, the quantum yield is seen to change only within a narrow interval in such an ensemble.

physics.bio-ph↗

arXiv2001

Excitons in a Photosynthetic Light-Harvesting System: A Combined Molecular Dynamics/Quantum Chemistry and Polaron Model Study

The dynamics of pigment-pigment and pigment-protein interactions in light-harvesting complexes is studied with a novel approach which combines molecular dynamics (MD) simulations with quantum chemistry (QC) calculations. The MD simulations of an LH-II complex, solvated and embedded in a lipid bilayer at physiological conditions (with total system size of 87,055 atoms) revealed a pathway of a water molecule into the B800 binding site, as well as increased dimerization within the B850 BChl ring, as compared to the dimerization found for the crystal structure. The fluctuations of pigment (B850 BChl) excitation energies, as a function of time, were determined via ab initio QC calculations based on the geometries that emerged from the MD simulations. From the results of these calculations we constructed a time-dependent Hamiltonian of the B850 exciton system from which we determined the linear absorption spectrum. Finally, a polaron model is introduced to describe quantum mechanically both the excitonic and vibrational (phonon) degrees of freedom. The exciton-phonon coupling that enters into the polaron model, and the corresponding phonon spectral function are derived from the MD/QC simulations. It is demonstrated that, in the framework of the polaron model, the absorption spectrum of the B850 excitons can be calculated from the autocorrelation function of the excitation energies of individual BChls, which is readily available from the combined MD/QC simulations. The obtained result is in good agreement with the experimentally measured absorption spectrum.

physics.bio-ph↗

arXiv1999

Unbinding of Retinoic Acid from its Receptor Studied by Steered Molecular Dynamics

Retinoic acid receptor (RAR) is a ligand-dependent transcription factor that regulates the expression of genes involved in cell growth, differentiation, and development. Binding of the retinoic acid hormone to RAR is accompanied by conformational changes in the protein which induce transactivation or transrepression of the target genes. In this paper we present a study of the hormone binding/unbinding process in order to clarify the role of some of the amino acid contacts and identify possible pathways of the all-trans retinoic acid binding/unbinding to/from human retinoic acid receptor (hRAR)-g. Three possible pathways were explored using steered molecular dynamics simulations. Unbinding was induced on a time scale of 1 ns by applying external forces to the hormone. The simulations suggest that the hormone may employ one pathway for binding and an alternative "back door" pathway for unbinding.

physics.bio-ph↗

arXiv1997

Introduction to the Diffusion Monte Carlo Method

A self-contained and tutorial presentation of the diffusion Monte Carlo method for determining the ground state energy and wave function of quantum systems is provided. First, the theoretical basis of the method is derived and then a numerical algorithm is formulated. The algorithm is applied to determine the ground state of the harmonic oscillator, the Morse oscillator, the hydrogen atom, and the electronic ground state of the H2+ ion and of the H2 molecule. A computer program on which the sample calculations are based is available upon request.

physics.comp-ph↗

arXiv1997

Boundary Integral Method for Stationary States of Two-Dimensional Quantum Systems

The boundary integral method for calculating the stationary states of a quantum particle in nano-devices and quantum billiards is presented in detail at an elementary level. According to the method, wave functions inside the domain of the device or billiard are expressed in terms of line integrals of the wave function and its normal derivative along the domain's boundary; the respective energy eigenvalues are obtained as the roots of Fredholm determinants. Numerical implementations of the method are described and applied to determine the energy level statistics of billiards with circular and stadium shapes and demonstrate the quantum mechanical characteristics of chaotic motion. The treatment of other examples as well as the advantages and limitations of the boundary integral method are discussed.

physics.comp-ph↗