Sadegh Faramarzi
West Virginia University, C. Eugene Bennett Dept. of Chemistry, Graduate Student
Micelles are spherical assemblies of detergent molecules that form in aqueous solutions.The hydrophilic head of each molecule faces water on the outside of the sphere and the hydrophobic tail of the molecule points toward the center of... more
Micelles are spherical assemblies of detergent molecules that form in aqueous solutions.The hydrophilic head of each molecule faces water on the outside of the sphere and the hydrophobic tail of the molecule points toward the center of the micelle. While detergent micelles are commonly used to mimic cell membranes during experimental work on membrane proteins, their biophysical properties are not well understood at the atomistic level. The present work focuses on all atom molecular dynamics simulations of the detergent molecule dodecylmaltoside (DDM). We have investigated the effects of starting configurations and total number of molecules in the simulation (above and below the aggregation number) using pre- formed micelle arrangements consisting of 60, 80, 100, 130, 150, and 200 DDM molecules and random assortment arrangements of 60, 110, 200, and 220 DDM molecules. Results to be presented include validation of the CHARMM force field for DDM, aggregation number, and radius of gyrat...
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Supplementary Information for "Closed-loop neuromodulation for clustering neuronal populations"
ObjectiveThe objective of this study was to measure the effect of micromagnetic stimulation (μMS) on hippocampal neurons, by using single microcoil (μcoil) prototype, Magnetic Pen (MagPen). MagPen will be used to stimulate the CA3 region... more
ObjectiveThe objective of this study was to measure the effect of micromagnetic stimulation (μMS) on hippocampal neurons, by using single microcoil (μcoil) 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 the μcoil will be demonstrated. Finally, the optimal stimulation frequency of the current driving the μcoil to minimize power will be estimated.ApproachA biocompatible, watertight, non-corrosive prototype, MagPen was built, and customized such that it is easy to adjust the orientation of the μcoil and its distance over the hippocampal tissue in an in vitro recording setting. Finite element modeling (FEM) of the μcoil design was performed to estimate the spatial profiles of the magnetic flux density (in T) and the induced electr...
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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... more
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 in vivo methods for determining BBB permeability is rodent log BB; however, like most in vivo 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. The in vivo BBB permeability data were harvested for 921 compounds from publicly available literature, non-proprietary drug approval packages, and University of Washington’s Drug Interaction Database. The cross-validation performance statistics for the BBB models ranged from 82 to 85% in sensitivity and 80–83% in negative predictivity. Additionally, the performance of newly developed models was assessed using an ext...
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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... more
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. As an alternative to CR, we present a closed-loop control setup that desynchronizes neurons in brain slices by inducing clusters using a single electrode. Our setup uses calcium fluorescence imaging to extract carbachol-induced neuronal oscillations in real time. To determine the appropriate stimulation waveform for inducing clusters in a population of neurons, we calculate the phase of the neuronal populations and then estimate the phase response curve (PRC) of those populations to electrical stimulation. The phase and PRC are th...
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Optimized desublimation of 2,4-diaminotoluene (4-methylbenzene-1,3-diamine) formed its ultrapure crystals. The collected crystals were analyzed by X-ray crystallography and then directly consumed in a condensation reaction with... more
Optimized desublimation of 2,4-diaminotoluene (4-methylbenzene-1,3-diamine) formed its ultrapure crystals. The collected crystals were analyzed by X-ray crystallography and then directly consumed in a condensation reaction with paraformaldehyde that resulted in the formation of Hunlich’s base. The subsequent one-pot diazotization and coupling reactions produced a new bisazo analog of Troger’s base in the maximum possible compliance with the principles of green chemistry. The obtained bisazo product was found to be a durable and affordable building block suitable for use in the design of light-driven molecular machines.
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Molecular Dynamics (MD) simulations are being used to model the aggregation of detergents into spherical assemblies called micelles. Detergent micelles can be used experimentally to study membrane proteins. In the present study, we are... more
Molecular Dynamics (MD) simulations are being used to model the aggregation of detergents into spherical assemblies called micelles. Detergent micelles can be used experimentally to study membrane proteins. In the present study, we are investigating micelle formation in dodecyl β-D-maltoside (DDM) detergents with a longer-term goal of understanding how the nature of the detergent micelle influences the properties of the membrane protein proteorhodopsin. Proteorhodopsin captures sunlight and stores it in a proton gradient that the cell can use to directly drive ATP synthesis; in marine environments, this protein may be responsible for 10-15% of what was once thought to be photosynthesis. Nanoscale Molecular Dynamics (NAMD) and Visual Molecular Dynamics (VMD) software programs are being run on a high-speed Linux workstation at Fairmont State University and the High Performance Computing systems at West Virginia University. Simulation results are analyzed to generate quantitative data ...
ObjectiveThe objective of this study was to measure the effect of micromagnetic stimulation (μMS) on hippocampal neurons, by using single microcoil (μcoil) prototype, Magnetic Pen (MagPen). MagPen will be used to stimulate the CA3 region... more
ObjectiveThe objective of this study was to measure the effect of micromagnetic stimulation (μMS) on hippocampal neurons, by using single microcoil (μcoil) 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 the μcoil will be demonstrated. Finally, the optimal stimulation frequency of the current driving the μcoil to minimize power will be estimated.ApproachA biocompatible, watertight, non-corrosive prototype, MagPen was built, and customized such that it is easy to adjust the orientation of the μcoil and its distance over the hippocampal tissue in an in vitro recording setting. Finite element modeling (FEM) of the μcoil design was performed to estimate the spatial profiles of the magnetic flux density (in T) and the induced electr...
Research Interests:
Bisazo Tröger base analogs are claw-looking molecules that carry two identical but independent photoswitching groups. These bisazo compounds, like dual switches, can be at EE, EZ, and ZZ photoisomerization states while the ∧-shape void of... more
Bisazo Tröger base analogs are claw-looking molecules that carry two identical but independent photoswitching groups. These bisazo compounds, like dual switches, can be at EE, EZ, and ZZ photoisomerization states while the ∧-shape void of Tröger base scaffold may also introduce an additional possibility of stereoisomerism by holding the photoisomerizable groups in endo or exo positions. To date, the exact molecular geometries of the isomerizable analogs of Tröger's base have not been elaborated. Owing to the special features and potential applications of these molecules, herein their photoisomerization is probed. The gleaned data from 15N isotope labeling and a variety of spectroscopic, spectrophotometric, crystallographic, and computational techniques have revealed the structure of the studied photoisomers and suggested their use in the design of molecular pull and push mechanisms, light driven actuators, and artificial muscles.
Research Interests: Organic Chemistry, Stable Isotope Analysis, NMR Spectroscopy, Anisotropy, Organic Synthesis, and 11 moreMolecular Machine, Molecular Motors, Artificial Molecular Motors, Magnetic Anisotropy, THEORETICAL AND COMPUTATIONAL CHEMISTRY, Molecular Design, Molecular Switches, Preperation of Azo Compound, Azo Dyes, Electronic Transport In Molecules, and Molecular Structure
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... more
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. However, it is unclear if the proton donor in PR, E108, utilizes the same latch mechanism to become internally hydrated. Here, we used molecular dynamics simulations to model the changes in internal hydration of the blue variant of PR during photoactivation with the proton donor in protonated and deprotonated states. We find that there is a stark contrast in the levels of internal hydration of the cytoplasmic half of PR based on the protonation state of E108. Instead of a latch mechanism, depr...
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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... more
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. In addition, we show that hydration of the micelle interior is limited; however, flexibility of the acyl chains leads to dynamic encounters with the solvated outer shell of the micelle, providing an explanation for long-standing differences in models of micelle hydration. Altogether, our results provide fundamental understanding of physical characteristics of micelles that can be utilized to study other types of detergents and proteomicelle complexes.
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Bisazo Tröger base analogs are claw-looking molecules that carry two identical but independent photoswitching groups. These bisazo compounds, like dual switches, can be at EE, EZ, and ZZ photoisomerization states while the ∧-shape void of... more
Bisazo Tröger base analogs are claw-looking molecules that carry two identical but independent photoswitching groups. These bisazo compounds, like dual switches, can be at EE, EZ, and ZZ photoisomerization states while the ∧-shape void of Tröger base scaffold may also introduce an additional possibility of stereoisomerism by holding the photoisomerizable groups in endo or exo positions. To date, the exact molecular geometries of the isomerizable analogs of Tröger's base have not been elaborated. Owing to the special features and potential applications of these molecules, herein their photoisomerization is probed. The gleaned data from 15N isotope labeling and a variety of spectroscopic, spectrophotometric, crystallographic, and computational techniques have revealed the structure of the studied photoisomers and suggested their use in the design of molecular pull and push mechanisms, light driven actuators, and artificial muscles.