Long-Time Scale Simulations Reveal Key Dynamics That Drive the Onset of the N State in the Proteorhodopsin Photocycle.

Proteorhodopsin (PR) is a microbial proton pump that plays a significant role in phototrophy of bacteria in marine environments. Fundamental understanding of the structure-function relationship that drives proton pumping in PR has largely been elusive due to a lack of high-resolution structures of the photointermediates in the PR photocycle. Extending upon previous work, we used long-time scale molecular dynamics (MD) simulations to characterize the M state of the blue variant of PR, which represents the first proton transfer that takes place in the photocycle.

Development of QSAR models to predict blood-brain barrier permeability.

Assessing drug permeability across the blood-brain barrier (BBB) is important when evaluating the abuse potential of new pharmaceuticals as well as developing novel therapeutics that target central nervous system disorders. One of the gold-standard methods for determining BBB permeability is rodent log BB; however, like most methods, it is time-consuming and expensive. In the present study, two statistical-based quantitative structure-activity relationship (QSAR) models were developed to predict BBB permeability of drugs based on their chemical structure.

Strength-frequency curve for micromagnetic neurostimulation through excitatory postsynaptic potentials (EPSPs) on rat hippocampal neurons and numerical modeling of magnetic microcoil (coil).

The objective of this study was to measure the effect of micromagnetic stimulation (MS) on hippocampal neurons, by using single microcoil (coil) prototype, magnetic pen (MagPen). MagPen will be used to stimulate the CA3 region magnetically and excitatory post synaptic potential (EPSP) response measurements will be made from the CA1 region. The threshold for micromagnetic neurostimulation as a function of stimulation frequency of the current driving thecoil will be demonstrated.

Closed-Loop neuromodulation for clustering neuronal populations.

Pathological synchronization of neurons is associated with symptoms of movement disorders, such as Parkinson's disease and essential tremor. High-frequency deep brain stimulation (DBS) suppresses symptoms, presumably through the desynchronization of neurons. Coordinated reset (CR) delivers trains of high-frequency stimuli to different regions in the brain through multiple electrodes and may have more persistent therapeutic effects than conventional DBS.

Synchronization of heterogeneous oscillator populations in response to weak and strong coupling.

Synchronous behavior of a population of chemical oscillators is analyzed in the presence of both weak and strong coupling. In each case, we derive upper bounds on the critical coupling strength which are valid for arbitrary populations of nonlinear, heterogeneous oscillators. For weak perturbations, infinitesimal phase response curves are used to characterize the response to coupling, and graph theoretical techniques are used to predict synchronization.

Allosteric Effects of the Proton Donor on the Microbial Proton Pump Proteorhodopsin.

Proteorhodopsin (PR) is a microbial proton pump that is ubiquitous in marine environments and may play an important role in the oceanic carbon cycle. Photoisomerization of the retinal chromophore in PR leads to a series of proton transfers between specific acidic amino acid residues and the Schiff base of retinal, culminating in a proton motive force to facilitate ATP synthesis. The proton donor in a similar retinal protein, bacteriorhodopsin, acts as a latch to allow the influx of bulk water.

Molecular Dynamics Simulations as a Tool for Accurate Determination of Surfactant Micelle Properties.

Molecular dynamics (MD) simulations were used to characterize the equilibrium size, shape, hydration, and self-assembly of dodecylphosphocholine (DPC) and dodecyl-β-D-maltoside (DDM) micelles. We show that DPC molecules self-assemble to form micelles with sizes within the range reported in the experimental literature. The equilibrium shape of DPC and DDM micelles as well as associated micellar radii are in agreement with small-angle X-ray scattering (SAXS) experiments and theoretical packing parameters.

Desynchronization of stochastically synchronized chemical oscillators.

Experimental and theoretical studies are presented on the design of perturbations that enhance desynchronization in populations of oscillators that are synchronized by periodic entrainment. A phase reduction approach is used to determine optimal perturbation timing based upon experimentally measured phase response curves. The effectiveness of the perturbation waveforms is tested experimentally in populations of periodically and stochastically synchronized chemical oscillators.