Biological and Chemical Physics Commons^™

Hi-Fidelity Simulation Of The Self-Assembly And Dynamics Of Colloids And Polymeric Solutions With Long Range Interactions, Mahdy Malekzadeh Moghani

Doctoral Dissertations

Modeling the equilibrium properties and dynamic response of the colloidal and polymeric solutions provides valuable insight into numerous biological and industrial processes and facilitates development of novel technologies. To this end, the centerpiece of this research is to incorporate the long range electrostatic or hydrodynamic interactions via computationally efficient algorithms and to investigate the effect of these interactions on the self-assembly of colloidal particles and dynamic properties of polymeric solutions. Specifically, self-assembly of a new class of materials, namely bipolar Janus nano-particles, is investigated via molecular dynamic simulation in order to establish the relationship between individual particle characteristics, such as …

Competitive Evaluation Of Data Mining Algorithms For Use In Cassification Of Leukocyte Subtypes With Raman Microspectroscopy, Adrian Maguire, I. Vega-Carrascal, Jane Bryant, Lisa White, Orla Howe, Fiona Lyng, Aidan Meade

Articles

Raman microspectroscopy has been investigated for some time for use in label-free cell sorting devices. These approaches require coupling of the Raman spectrometer to complex data mining algorithms for identification of cellular subtypes such as the leukocyte subpopulations of lymphocytes and monocytes. In this study, three distinct multivariate classification approaches, (PCA-LDA, SVMs and Random Forests) are developed and tested on their ability to classify the cellular subtype in extracted peripheral blood mononuclear cells (T-cell lymphocytes from myeloid cells), and are evaluated in terms of their respective classification performance. A strategy for optimisation of each of the classification algorithm is presented …

Single Molecule Studies Of A Short Rna, Peker Milas

Doctoral Dissertations

The material related with orientation of Cyanine dyes and their behavior at the ends of duplex RNA is also documented in [110]. Cyanine dyes are widely used to study the folding and structural transformations of nucleic acids using fluorescence resonance energy transfer (FRET). The extent to which FRET can be used to extract inter- and intra-molecular distances has been the subject of considerable debate in the literature; the contribution of dye and linker dynamics to the observed FRET signal is particularly troublesome. We used molecular dynamics (MD) simulations to study the dynamics of the indocarbocyanine dyes Cy3 and Cy5 attached …

The Impact Of Membrane Tension On Phase Separation And Solid Domain Properties In Model Multicomponent Vesicles, Dong Chen

Doctoral Dissertations

Multicomponent phospholipid membranes provide an ideal model to study the complex phase behavior of biological membranes. Giant unilamellar vesicles (GUV) formed by mixtures of two or more phospholipids have particular merit as model membranes because of their simplicity, operability, and ease of viewing phase separation and testing membrane mechanics. Until the research in this thesis, biochemistry and biophysical studies of phase separation in phospholipid membranes primarily addressed the influence of membrane composition on the transition temperatures and domain shapes. This thesis focuses on a commonly neglected variable - membrane tension, analogous to pressure in bulk materials, as an important parameter …

Rational Design Of Small-Molecule Stabilizers Of Spermine Synthase Dimer By Virtual Screening And Free Energy-Based Approach, Zhe Zhang, Virginie Martiny, David Lagorce, Yoshihiko Ikeguchi, Emil Alexov, Maria A. Miteva

Publications

Snyder-Robinson Syndrome (SRS) is a rare mental retardation disorder which is caused by the malfunctioning of an enzyme, the spermine synthase (SMS), which functions as a homo-dimer. The malfunctioning of SMS in SRS patients is associated with several identified missense mutations that occur away from the active site. This investigation deals with a particular SRS-causing mutation, the G56S mutation, which was shown computationally and experimentally to destabilize the SMS homo-dimer and thus to abolish SMS enzymatic activity. As a proof-of-concept, we explore the possibility to restore the enzymatic activity of the malfunctioning SMS mutant G56S by stabilizing the dimer through …

Heterogeneous Rotational Diffusion Of A Fluorescent Probe In Lipid Monolayers, Christina M. Othon

Christina M Othon

The rotational correlation time of the lipid probe 1-palmitoyl-2-{6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl}-sn-glycero-3-phosphocholine (NBD-PC) is measured using fluorescence anisotropy for two lipid species. We measure the rotational diffusion in a monolayer of 1,2-Didecanoyl-sn-glycero-3-phosphocholine (DPPC) which displays a phase transition at room temperature from the liquid expanded to the liquid-condensed phase. The constant rotational diffusion of the probe throughout the phase transition reflects the measurement of dynamics in only the liquid-expanded phase. We contrast the dynamic changes during this phase coexistence to the continuous density increase observed in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) at room temperature. We observe a non-exponential decay of the probe diffusion consistent with heterogeneity …

Structure And Elasticity Of Lipid Membranes With Genistein And Daidzein Bioflavinoids Using X-Ray Scattering And Md Simulations., Mohit Raghunathan, Yuriy Zubovski, Richard Venable, Richard Pastor, John Nagle, Stephanie Tristram-Nagle

Prof. Stephanie Tristram-Nagle Ph.D.

This work reports the effects of the bioflavinoids genistein and daidzein on lipid bilayers as determined by volume measurements, X-ray scattering, and molecular dynamics simulations. The experimental and simulated total molecular volumes were found to be in outstanding agreement with each other before the addition of genistein and daidzein and also after their addition. Both bioflavinoids inserted into the hydrocarbon region of both DOPC and diphytanoylPC near the carbonyls of the lipids and both decreased the bilayer thicknesses. The long axes of both bioflavinoids were oriented nearly parallel to the plane of the bilayer with their carbonyl groups preferentially pointed …

Protein Nano-Object Integrator: Generating Atomic-Style Objects For Use In Molecular Biophysics, Nicholas Smith

All Theses

As researchers obtain access to greater and greater amounts of computational power, focus has shifted towards modeling macroscopic objects while still maintaining atomic-level details. The Protein Nano-Object Integrator (ProNOI) presented here has been designed to provide a streamlined solution for creating and designing macro-scale objects with atomic-level details to be used in molecular simulations and tools. To accomplish this, two different interfaces were developed: a Protein Data Bank (PDB), PDB-focused interface for generating regularly-shaped three-dimensional atomic objects and a 2D image-based interface for tracing images with irregularly shaped objects and then extracting three-dimensional models from these images. Each interface is …

Problm Web Server: Protein And Membrane Placement And Orientation Package, Taylor Kimmett, Nicholas Smith, Shawn Witham, Marharyta Petukh, Subhra Sarkar, Emil Alexov

Publications

The 3D structures of membrane proteins are typically determined without the presence of a lipid bilayer. For the purpose of studying the role of membranes on the wild type characteristics of the corresponding protein, determining the position and orientation of transmembrane proteins within a membrane environment is highly desirable. Here we report a geometry-based approach to automatically insert a membrane protein with a known 3D structure into pregenerated lipid bilayer membranes with various dimensions and lipid compositions or into a pseudomembrane. The pseudomembrane is built using the Protein Nano-Object Integrator which generates a parallelepiped of user-specified dimensions made up of …

A Non-Contrast Magnetic Resonance Imaging Technique To Assess Blood-Brain Barrier Permeability, Harini Pandithasekera

Electronic Thesis and Dissertation Repository

The Blood-brain barrier (BBB) regulates the entry of compounds between the blood and the brain, thus plays an important role in brain homeostasis. Studies indicate in disease states such as Alzheimer’s the BBB integrity is compromised. The motive of this project is to investigate the sensitivity of the diffusion-weighted arterial spin labeling (DW-ASL) technique to detect water exchange. Testing the sensitivity requires a reliable method of opening the barrier at specific locations of the brain. Here, a unique technology named focused ultrasound (FUS) has been used to mimic a compromised BBB environment.

A series of experiments were conducted in a …

Binding Of Solvated Peptide (Eplqlkm) With A Graphene Sheet Via Simulated Coarse-Grained Approach, Somayyeh Sheikholeslami, R. B. Pandey, Nadiya Dragneva, Wely Floriano, Oleg Rubel, Stephen A. Barr, Zhifeng Kuang, Rajiv Berry, Rajesh Naik, Barry Farmer

Faculty Publications

Binding of a solvated peptide A1 (¹E ²P ³L ⁴Q ⁵L ⁶K ⁷M) with a graphene sheet is studied by a coarse-grained computer simulation involving input from three independent simulated interaction potentials in hierarchy. A number of local and global physical quantities such as energy, mobility, and binding profiles and radius of gyration of peptides are examined as a function of temperature (T). Quantitative differences (e.g., the extent of binding within a temperature range) and qualitative similarities are observed in results from three simulated potentials. Differences in variations of both local and …

Does Protein Folding Exhibit Self-Organized Criticality?, Addison Wisthoff

Senior Theses

Proteins are known to fold into tertiary structures that determine their functionality in living organisms. By understanding the general features of this folding process, that are independent of specific proteins, folding can be better understood. Self-organized critical systems exhibit behavior that scales with system size. In this project, I wrote a simulation of a simplistic three-dimensional cubic lattice protein model. The model consisted of only two different types of amino acids, one being hydrophobic and the other hydrophilic, known as the HP model. To identify self-organized criticality in proteins, there must be clear signs of power law behavior in the …

Computational And Experimental Approaches To Reveal The Effects Of Single Nucleotide Polymorphisms With Respect To Disease Diagnostics, Tugba G. Kucukkal, Ye Yang, Susan C. Chapman, Weiguo Cao, Emil Alexov

Publications

DNA mutations are the cause of many human diseases and they are the reason for natural differences among individuals by affecting the structure, function, interactions, and other properties of DNA and expressed proteins. The ability to predict whether a given mutation is disease-causing or harmless is of great importance for the early detection of patients with a high risk of developing a particular disease and would pave the way for personalized medicine and diagnostics. Here we review existing methods and techniques to study and predict the effects of DNA mutations from three different perspectives: in silico, in vitro and …

Chronic Beryllium Disease: Revealing The Role Of Beryllium Ion And Small Peptides Binding To Hla-Dp2, Marharyta Petukh, Bohua Wu, Shannon Stefl, Nick Smith, David Hyde-Volpe, Li Wang, Emil Alexov

Publications

Chronic Beryllium (Be) Disease (CBD) is a granulomatous disorder that predominantly affects the lung. The CBD is caused by Be exposure of individuals carrying the HLA-DP2 protein of the major histocompatibility complex class II (MHCII). While the involvement of Be in the development of CBD is obvious and the binding site and the sequence of Be and peptide binding were recently experimentally revealed [1], the interplay between induced conformational changes and the changes of the peptide binding affinity in presence of Be were not investigated. Here we carry out in silico modeling and predict the Be binding to be within …

On The Modeling Of Polar Component Of Solvation Energy Using Smooth Gaussian-Based Dielectric Function, Lin Li, Chuan Li, Emil Alexov

Publications

Traditional implicit methods for modeling electrostatics in biomolecules use a two-dielectric approach: a biomolecule is assigned low dielectric constant while the water phase is considered as a high dielectric constant medium. However, such an approach treats the biomolecule-water interface as a sharp dielectric border between two homogeneous dielectric media and does not account for inhomogeneous dielectric properties of the macromolecule as well. Recently we reported a new development, a smooth Gaussian-based dielectric function which treats the entire system, the solute and the water phase, as inhomogeneous dielectric medium (J Chem Theory Comput. 2013 Apr 9; 9(4): 2126-2136.). Here we examine …

On The Electrostatic Properties Of Homodimeric Proteins, Brandon Campbell, Marharyta Petukh, Emil Alexov, Chuan Li

Publications

A large fraction of proteins function as homodimers, but it is not always clear why the dimerization is important for functionality since frequently each monomer possesses a distinctive active site. Recent work (PLoS Computational Biology, 9(2), e1002924) indicates that homodimerization may be important for forming an electrostatic funnel in the spermine synthase homodimer which guides changed substrates toward the active centers. This prompted us to investigate the electrostatic properties of a large set of homodimeric proteins and resulted in an observation that in a vast majority of the cases the dimerization indeed results in specific electrostatic features, although not necessarily …

A Novel P.Leu(381)Phe Mutation In Presenilin 1 Is Associated With Very Early Onset And Unusually Fast Progressing Dementia As Well As Lysosomal Inclusions Typically Seen In Kufs Disease, Natalia Dolzhanskaya, Michael A. Gonzalez, Fiorella Sperziani, Shannon Stefl, Jeffrey Messing, Guang Y. Wen, Emil Alexov, S Stephan Zuchner, Milen Velinov

Publications

Whole exome sequencing in a family with suspected dominant Kufs disease identified a novel Presenilin 1 mutation p.Leu(381)Phe in three brothers who, along with their father, developed progressive dementia and motor deficits in their early 30s. All affected relatives had unusually rapid disease progression (on average 3.6 years from disease onset to death). In silico analysis of mutation p.Leu(381)Phe predicted more detrimental effects when compared to the common Presenilin 1 mutation p.Glu(280)Ala. Electron microscopy study of peripheral fibroblast cells of the proband showed lysosomal inclusions typical for Kufs disease. However his brain autopsy demonstrated typical changes of Alzheimer disease.

Voltage Gating Interactions Of The Protein Lysenin With Metal Ions In An Artificial Lipid Bilayer, Tyler Clark, Sheenah Bryant, Steve Rossland, Eric Krueger, Charles Hanna, Daniel Fologea

College of Arts and Sciences Presentations

Non-specific ion conductance channels can be formed in lipid membranes by the poreforming toxin lysenin. These channels are voltage regulated and are responsive to changes in metal ion concentration. In our research, we studied the effects of metal ion concentration on the lysenin channel’s voltage regulated gating, using both multivalent and monovalent metals. A model was developed to explain the apparent subunit cooperativity within the lysenin channel. The model allows for the complex reaction to changing concentration of metal ions, and offers knowledge of the lysenin channel’s internal workings.

Searching For Effective Forces In Laboratory Insect Swarms, James G. Puckett, Douglas H. Kelley, Nicholas T. Ouellette

Physics and Astronomy Faculty Publications

Collective animal behaviour is often modeled by systems of agents that interact via effective social forces, including short-range repulsion and long-range attraction. We search for evidence of such effective forces by studying laboratory swarms of the flying midge Chironomus riparius. Using multi-camera stereoimaging and particle-tracking techniques, we record three-dimensional trajectories for all the individuals in the swarm. Acceleration measurements show a clear short-range repulsion, which we confirm by considering the spatial statistics of the midges, but no conclusive long-range interactions. Measurements of the mean free path of the insects also suggest that individuals are on average very weakly coupled, but …

Structural Flexibility And Oxygen Diffusion Pathways In Monomeric Fluorescent Proteins, Chola K. Regmi

FIU Electronic Theses and Dissertations

Fluorescent proteins are valuable tools as biochemical markers for studying cellular processes. Red fluorescent proteins (RFPs) are highly desirable for in vivo applications because they absorb and emit light in the red region of the spectrum where cellular autofluorescence is low. The naturally occurring fluorescent proteins with emission peaks in this region of the spectrum occur in dimeric or tetrameric forms. The development of mutant monomeric variants of RFPs has resulted in several novel FPs known as mFruits. Though oxygen is required for maturation of the chromophore, it is known that photobleaching of FPs is oxygen sensitive, and oxygen-free conditions …