# Rozita LaghaeiCarnegie Mellon University | CMU · Pittsburgh Supercomputing Center

Rozita Laghaei

PhD

## About

30

Publications

5,815

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730

Citations

Introduction

Computational Neuroscience; Computational biophysics

Additional affiliations

May 2015 - present

December 2010 - May 2015

**University of Pittsburgh**

Position

- Researcher

February 2007 - December 2010

## Publications

Publications (30)

Influx of ferrous ions from the cytoplasm through 3-fold pores in the shell of ferritin protein is computed using a 3-dimensional Poisson-Nernst-Planck electrodiffusion model, with inputs such as the pore structure and the diffusivity profile of permeant Fe(2+) ions extracted from all-atom Molecular Dynamics (MD) simulations. These calculations suc...

The general mechanism of calcium-triggered chemical transmitter release from neuronal synapses has been intensely studied, is well-known, and highly conserved between species and synapses across the nervous system. However, the structural and functional details within each transmitter release site (or active zone) are difficult to study in living t...

The action potential (AP) waveform controls the opening of voltage-gated calcium channels and contributes to the driving force for calcium ion flux that triggers neurotransmission at presynaptic nerve terminals. Although the frog neuromuscular junction (NMJ) has long been a model synapse for the study of neurotransmission, its presynaptic AP wavefo...

We carry out extensive computer simulations to study the phase equilibrium, thermodynamics, and diffusion coefficient of three-center Lennard-Jones (3CLJ) fluids with an emphasis on the effects of bond angle on these properties. We take into account several bond angles ranging from θ0 = 60 to 180 degrees and two equilibrium bond elongations le = 1....

We have investigated the impact of transmitter release site (active zone; AZ) structure on synaptic function by physically rearranging the individual AZ elements in a previously published frog neuromuscular junction (NMJ) AZ model into the organization observed in a mouse NMJ AZ. We have used this strategy, purposefully without changing the propert...

The spatio-temporal calcium dynamics within presynaptic neurotransmitter release sites (active zones, AZs) at the time of synaptic vesicle fusion is critical for neurotransmitter release. Specifically, the relative arrangement and density of voltage gated calcium channels (VGCCs) as well as the concentration of calcium buffering proteins can play a...

At present, the three-dimensional structure of the multimeric paracellular claudin pore is unknown. Using extant biophysical data concerning the size of the pore and permeation of water and cations through it, two three-dimensional models of the pore are constructed in silico. Molecular Dynamics (MD) calculations are then performed to compute water...

In recent years, much effort has focused on the early stages of aggregation and the formation of amyloid oligomers. Aggregation processes for these proteins are complex and their non-equilibrium nature makes any experimental study very difficult. Under these conditions, simulations provide a useful alternative for understanding the dynamics of the...

We study via all atom classical molecular dynamics (MD) simulation the process of uptake of ferrous ions (Fe(2+) ) into the human ferritin protein and the catalytic ferroxidase sites via pores ("channels") in the interior of the protein. We observe that the 3-fold hydrophilic channels serve as the main entrance pathway for the Fe(2+) ions. The bind...

We study the mechanism of vacancy migration and phase transitions of 3D crystalline colloidal arrays (CCA) using Langevin dynamics simulations. We calculate the self-diffusion coefficient of the colloid particles and the diffusion constant for vacancies as a function of temperature and DLVO potential parameters. We investigate the phase behavior of...

The Amyloid-beta protein is related to Alzheimer's disease and various experiments have shown that oligomers as small as the dimer are cytotoxic. Two alloforms are mainly produced: Aβ1-40 and Aβ1-42. They have very different oligomer distributions, and it was recently suggested, from experimental studies, that this variation may originate from stru...

Several proteins possess a segment of amino acids composed of successive glutamines. In many, this segment affects the native folding when expanded above 35 to 40 glutamines. Such effect is associated to neurodegenerative diseases such as Huntington's in which the huntingtin protein misfold. As the huntingtin protein has over 3000 amino acids, it i...

The loss of the insulin-producing β-cells in the pancreatic islets of Langerhans, responsible for type-II diabetes, is associated with islet amyloid deposits. The main component of these deposits is the amyloid fibrils formed by the 37-residue human islet amyloid polypeptide (hIAPP also known as amylin). Although the fibrils are well characterized...

The human Islet amyloid polypeptide (hIAPP or amylin) is a 37-residue peptide hormone that is normally cosecreted with insulin by the pancreatic beta-cells. In patients with type 2 diabetes, hIAPP deposits as amyloid fibrils in the extracellular spaces of the pancreatic islets. Recent experimental studies show that the intramolecular disulfide bond...

Expansion of polyglutamine (polyQ) beyond the pathogenic threshold (35-40 Gln) is associated with several neurodegenerative diseases including Huntington's disease, several forms of spinocerebellar ataxias and spinobulbar muscular atrophy. To determine the structure of polyglutamine aggregates we perform replica-exchange molecular dynamics simulati...

Current approaches aimed at determining the free energy surface of all-atom medium-size proteins in explicit solvent are slow and are not sufficient to converge to equilibrium properties. To ensure a proper sampling of the configurational space, it is preferable to use reduced representations such as implicit solvent and/or coarse-grained protein m...

A newly proposed theory [R. Laghaei et al., J. Chem. Phys. 124, 154502 (2006)] was extended to polyatomics and applied to compute the density and temperature dependence of the effective site diameters of carbon disulfide fluids. The generic van der Waals (GvdW) theory was also extended to polyatomics in order to calculate the GvdW parameters and th...

A quantum mechanical derived ab initio interaction potential for the argon dimer was tested in molecular simulations to reproduce the thermophysical properties of the vapor-liquid phase equilibria using the Gibbs ensemble Monte Carlo simulations as well as the liquid and supercritical equation of state using the NVT Monte Carlo simulations. The ab...

In the previous papers applying the generic van der Waals equation of state the mean excluded volume was defined with the contact diameter of particles at which the potential energy is equal to zero-the size parameter in the case of the Lennard-Jones potential. This parameter appears as the upper limit of the integral for the generic van der Waals...

In this paper the thermal conductivity of the Lennard-Jones fluid is calculated by applying the combination of the density-fluctuation theory, the modified free volume theory of diffusion, and the generic van der Waals equation of state. A Monte Carlo simulation method is used to compute the equilibrium pair-correlation function necessary for compu...

The generalized Boltzmann equation for simple dense fluids gives rise to the stress tensor evolution equation as a constitutive equation of generalized hydrodynamics for fluids far removed from equilibrium. It is possible to derive a formula for the non-Newtonian shear viscosity of the simple fluid from the stress tensor evolution equation in a sui...

In this paper, we apply the Matteoli-Mansoori empirical formula for the pair correlation function of simple fluids obeying the Lennard-Jones potential to calculate reduced self-diffusion coefficients on the basis of the modified free volume theory. The self-diffusion coefficient thus computed as functions of temperature and density is compared with...

In previous work on the density fluctuation theory of transport coefficients of liquids, it was necessary to use empirical self-diffusion coefficients to calculate the transport coefficients (e.g., shear viscosity of carbon dioxide). In this work, the necessity of empirical input of the self-diffusion coefficients in the calculation of shear viscos...

The shear viscosity formula derived by the density fluctuation theory in previous papers is computed for argon, krypton, and methane by using the self-diffusion coefficients derived in the modified free volume theory with the help of the generic van der Waals equation of state. In the temperature regime near or above the critical temperature, the d...

Gibbs ensemble Monte Carlo simulations were used to test the ability of intermolecular pair potentials derived ab initio from quantum mechanical principles, enhanced by Axilrod-Teller triple-dipole interactions, to predict the vapor-liquid phase equilibria of pure neon, pure argon, and the binary mixtures neon-argon and argon-krypton. The interacti...

Köln, University, Diss., 2003 (Nicht für den Austausch).

## Projects

Projects (4)

Polymer chains grafted densely from one end to a solid substrate form a polymer brush. The morphology of these systems depends on different factors such as grafting density, temperature, PH etc. These parameters may change the brush height in a reversible manner and for this reason we call them “smart material”. They offer interesting possibilities for the design of devices whose shape could be programmable and adaptable. We use theory and computer simulation to study structure and different thermophysical properties of pure polymer brushes and their mixture with nanoparticles.

Abstract
Computational modeling is becoming very important in different fields of science. New technology and computational approaches permit modeling of increasingly complicated biological systems. For example, the cell modeling software MCell uses Monte Carlo algorithms to track the evolution of biochemical events in space and time for individual molecules. Details about molecular structures are ignored. Particles move according to a 3D Brownian-dynamics random walk and encounter boundaries and surface molecules as they diffuse which may result in chemical reactions governed by user specified mechanisms. As a case study we use MCell software to provide insight into many experimentally inaccessible aspects of synaptic function and the microscopic mechanisms underlying Ca2+ triggered synaptic vesicle release. The stochastic computational modeling using MCell can also be used to model and evaluation of a novel treatment for Lambert-Eaton Myasthenic Syndrome (LEMS), a neuromuscular disease that is characterized by motor nerve terminal weakness. This neurological disease is known to disrupt the normally well-organized active zone (AZ) and reduce the number of presynaptic calcium channels. This autoantibody mediated reduction of presynaptic calcium channels leads to severe muscle weakness.
MCell simulations can be used to evaluate the effects of the current treatment for LEMS (DAP alone which does not provide enough symptomatic relief for patients to return to normal activity and in combination with a newly developed calcium channel gating modifier (GV-58). These drugs are predicted to act synergistically to greatly enhance transmitter release. The use of MCell simulations in drug proper dose determination is an innovative approach that is predicted to extend beyond what can be done with physiological experiments alone.