Biomedical subjects

Markus Christen

Publications and source records attributed to Markus Christen.

9 recordsLinked to original sources

PubMed2006

On using oscillating time-dependent restraints in MD simulation.

The use of time-dependent restraints in molecular simulation in order to generate a conformational ensemble for molecules that is in accordance with measured ensemble averages for particular observable quantities is investigated. Using a model system consisting of liquid butane and the cyclic peptide antamanide the reproduction of particular average (3) J-coupling constant values in a molecular dynamics simulation is analysed. It is shown that the multiple-valuedness and the sizeable gradients of the Karplus curve relating (3) J-coupling constants measured in NMR experiments to the corresponding torsional-angle values cause severe problems when trying to restrain a (3) J-coupling constant to a value close to the extrema of the Karplus curve. The introduction of a factor oscillating with time into the restraining penalty function alleviates this problem and enhances the restrained conformational sampling.

Algorithms↗

PubMed2006

Odour encoding in olfactory neuronal networks beyond synchronization.

It has been suggested that odour encoding in olfactory systems occurs by synchronized firing in neuronal populations. Neurons correlated in terms of the Lempel-Ziv distance of spike trains and the sequential superparamagnetic clustering algorithm belong to the same cluster if they show similar, but not necessarily synchronous, firing patterns. Using multielectrode array recordings from the rat olfactory bulb, we have determined cluster incidence and stability in the neuronal network using both the Lempel-Ziv distance and a measure of synchronization. In the Lempel-Ziv paradigm, we found pronounced stabilization and destabilization effects in the neuronal network in response to odour presentation when compared with the synchronization paradigm. This suggests that synchronization alone may be insufficient for understanding olfactory coding.

Action Potentials↗

PubMed2006

Biomolecular modeling: Goals, problems, perspectives.

Computation based on molecular models is playing an increasingly important role in biology, biological chemistry, and biophysics. Since only a very limited number of properties of biomolecular systems is actually accessible to measurement by experimental means, computer simulation can complement experiment by providing not only averages, but also distributions and time series of any definable quantity, for example, conformational distributions or interactions between parts of systems. Present day biomolecular modeling is limited in its application by four main problems: 1) the force-field problem, 2) the search (sampling) problem, 3) the ensemble (sampling) problem, and 4) the experimental problem. These four problems are discussed and illustrated by practical examples. Perspectives are also outlined for pushing forward the limitations of biomolecular modeling.

Computer Simulation↗

PubMed2006

Sampling of rare events using hidden restraints.

A method to enhance sampling of rare events is presented. It makes use of distance or dihedral-angle restraints to overcome an energy barrier separating two metastable states or to stabilize a transition state between the two metastable states. In order not to perturb these metastable end states themselves, a prefactor is introduced into the restraining energy function, which smoothly increases the weight of this function from zero to one at the transition state or on top of the separating energy barrier and then decreases the weight again to zero at the final state. The method is combined with multi-configurational thermodynamic integration and applied to two biomolecular systems, which were difficult to treat using standard thermodynamic integration. As first example the free energy difference of a cyclic alpha-aminoxy-hexapeptide-ion complex upon changing the ion from Cl- to Na+ was calculated. A large conformational rearrangement of the peptide was necessary to accommodate this change. Stabilizing the transition state by (hidden) restraints facilitates that. As a second example, the free energy difference between the 4C1 and the 1C4 conformation of beta-D-glucopyranoside was calculated. In unrestrained simulations the change from the 4C1 into the 1C4 conformation was never observed because of the high energy barrier separating the two states. Using (hidden) restraints, the transition from the 4C1 into the 1C4 state and back could be enforced without perturbing the end states. As comparison, for the same transitions the potential of mean force as obtained by using dihedral-angle constraints is provided.

Journal Article↗

PubMed2006

Multigraining: an algorithm for simultaneous fine-grained and coarse-grained simulation of molecular systems.

A method to combine fine-grained and coarse-grained simulations is presented. The coarse-grained particles are described as virtual particles defined by the underlying fine-grained particles are described as virtual particles defined by the underlying fine-grained particles. The contribution of the two grain levels to the interaction between particles is specified by a grain-level parameter lambda. Setting lambda = 0 results in a completely fine-grained simulation, whereas lambda = 1 yields a simulation governed by the coarse-grained potential energy surface with small contributions to keep the fine-grained covalently bound particles together. Simulations at different lambda values may be coupled using the replica-exchange molecular dynamics method to achieve enhanced sampling at the fine-grained level.

Journal Article↗

PubMed2006

Measuring spike pattern reliability with the Lempel-Ziv-distance.

Spike train distance measures serve two purposes: to measure neuronal firing reliability, and to provide a metric with which spike trains can be classified. We introduce a novel spike train distance based on the Lempel-Ziv complexity that does not require the choice of arbitrary analysis parameters, is easy to implement, and computationally cheap. We determine firing reliability in vivo by calculating the deviation of the mean distance of spike trains obtained from multiple presentations of an identical stimulus from a Poisson reference. Using both the Lempel-Ziv-distance (LZ-distance) and a distance focussing on coincident firing, the pattern and timing reliability of neuronal firing is determined for spike data obtained along the visual information processing pathway of macaque monkey (LGN, simple and complex cells of V1, and area MT). In combination with the sequential superparamagnetic clustering algorithm, we show that the LZ-distance groups together spike trains with similar but not necessarily synchronized firing patterns. For both applications, we show how the LZ-distance gives additional insights, as it adds a new perspective on the problem of firing reliability determination and allows neuron classifications in cases, where other distance measures fail.

Algorithms↗

PubMed2005

An approximate but fast method to impose flexible distance constraints in molecular dynamics simulations.

A fast but approximative method to apply flexible constraints to bond lengths in molecular dynamics simulations is presented and the effects of the approximation are investigated. The method is not energy conserving, but coupling to a temperature bath results in stable simulations. The high frequencies from bond-length vibrations are successfully removed from the system while maintaining the flexibility of the bonds. As a test liquid neopentane is simulated at different pressures. Energetic and dynamic properties are not affected by the new flexible constraint simulation method.

Journal Article↗

PubMed2005

The GROMOS software for biomolecular simulation: GROMOS05.

We present the latest version of the Groningen Molecular Simulation program package, GROMOS05. It has been developed for the dynamical modelling of (bio)molecules using the methods of molecular dynamics, stochastic dynamics, and energy minimization. An overview of GROMOS05 is given, highlighting features not present in the last major release, GROMOS96. The organization of the program package is outlined and the included analysis package GROMOS++ is described. Finally, some applications illustrating the various available functionalities are presented.

Algorithms↗

PubMed2002

Collective bursting in layer IV. Synchronization by small thalamic inputs and recurrent connections.

Layer IV is believed to be the cortical signal amplifier, for example, of thalamic signals. A previous spiny stellate recurrent network model of this layer is made more realistic by the addition of inhibitory basket neurons. We study the persistence and characteristics of previously observed collective firing behavior, and investigate what additional features would need to be implemented to generate in vivo type neuronal firing. It is shown that neuronal activity is only coarsely synchronized within the network. By applying methods of noise-cleaning, it emerges that the firing of individual neurons is of low-dimensional hyperchaotic nature, as found in the analysis of measured cat in vivo spike trains. In order to reproduce in vivo firing patterns, it is sufficient to have time-varying thalamic input. Conclusions from low-dimensional hyperchaotic behavior of network-embedded neurons are drawn. We interpret observed in vivo pattern-sharpening features of stimuli and outline possible connections to epilepsy. From our results, it follows that emergent global behavior is likely to be the result of the interaction between comparably simple neuronal components, driven by input specificity.

Action Potentials↗