Biological and Chemical Physics Commons^™

Modeling Accuracy Matters: Aligning Molecular Dynamics With 2d Nmr Derived Noe Restraints, Milan Patel

Honors Scholar Theses

Among structural biology techniques, Nuclear Magnetic Resonance (NMR) provides a holistic view of structure that is close to protein structure in situ. Namely, NMR imaging allows for the solution state of the protein to be observed, derived from Nuclear Overhauser Effect restraints (NOEs). NOEs are a distance range in which hydrogen pairs are observed to stay within range of, and therefore experimental data which computational models can be compared against. To that end, we investigated the effects of adding the NOE restraints as distance restraints in Molecular Dynamics (MD) simulations on the 24 residue HP24stab derived villin headpiece subdomain to …

Self-Assembly Of Black Cumin Oil-Based Nanoemulsion On Various Surfactants: A Molecular Dynamics Study, Aulia Fikri Hidayat, Taufik Muhammad Fakih

Makara Journal of Science

Black cumin is commonly used as traditional medicine due to its wide range of pharmacological potential. Black cumin oil (BCO) was often prepared as nanoemulsion to improve its solubility, stability, and bioavailability. This study was conducted to investigate the molecular behavior as well as structural evolution of BCO-surfactant systems during self-assembly micellization using molecular dynamics (MD) simulations. Several BCO constituents and variations of surfactants were employed to model BCO-surfactant systems. 50 ns of MD simulations were performed to elucidate their evolution of structures and physicochemical properties during formation. Results showed that BCO-tween20 and BCO-lecithin were able to form spherical-shaped micelles …

Bridging The 12-6-4 Model And The Fluctuating Charge Model, Pengfei Li

Chemistry: Faculty Publications and Other Works

Metal ions play important roles in various biological systems. Molecular dynamics (MD) using classical force field has become a popular research tool to study biological systems at the atomic level. However, meaningful MD simulations require reliable models and parameters. Previously we showed that the 12-6 Lennard-Jones nonbonded model for ions could not reproduce the experimental hydration free energy (HFE) and ion-oxygen distance (IOD) values simultaneously when ion has a charge of +2 or higher. We discussed that this deficiency arises from the overlook of the ion-induced dipole interaction in the 12-6 model, and this term is proportional to 1/r …

Toward Improving Understanding Of The Structure And Biophysics Of Glycosaminoglycans, Elizabeth K. Whitmore

Electronic Theses and Dissertations

Glycosaminoglycans (GAGs) are the linear carbohydrate components of proteoglycans (PGs) that mediate PG bioactivities, including signal transduction, tissue morphogenesis, and matrix assembly. To understand GAG function, it is important to understand GAG structure and biophysics at atomic resolution. This is a challenge for existing experimental and computational methods because GAGs are heterogeneous, conformationally complex, and polydisperse, containing up to 200 monosaccharides. Molecular dynamics (MD) simulations come close to overcoming this challenge but are only feasible for short GAG polymers. To address this problem, we developed an algorithm that applies conformations from unbiased all-atom explicit-solvent MD simulations of short GAG polymers …

Computational Investigation Of The Interactions Between Bioactive Compounds And Biological Assemblies, Tye D. Martin

Biomedical Engineering ETDs

Small, biologically active molecules with unique properties and applications are potential solutions to a wide range of threats to global health including infectious agents and neurodegenerative disease. Experimental studies on a class of oligomeric p-phenylene ethynylenes (OPEs) have shown potential both as bioactive antimicrobials and fluorescent sensing agents for tracking amyloid-β (Aβ) aggregates found in Alzheimer’s Disease (AD). A second type of small molecule with potential applications in AD therapy, curcumin, has been found to interfere with Aβ fibril growth. Curcumin also attenuates Aβ-membrane interactions and Aβ toxicity. Our goal has been to use computational techniques to better understand the …

Structure And Thermodynamics Of Polyglutamine Peptides And Amyloid Fibrils Via Metadynamics And Molecular Dynamics Simulations, Riley Workman

Electronic Theses and Dissertations

Aggregation of polyglutamine (polyQ)-rich polypeptides in neurons is a marker for nine neurodegenerative diseases. The molecular process responsible for the formation of polyQ fibrils is not well understood and represents a growing area of study. To enable development of treatments that could interfere with aggregation of polyQ peptides, it is crucial to understand the molecular mechanisms by which polyQ peptides aggregate into fibrils. Many experimental techniques have been employed to probe polyQ aggregation, however, observations from these studies have not lead to a unified understanding of the properties of these systems, instead yielding competing, fragmented theories of polyQ aggregation. This …

Computational Analysis Of Poliovirus Structural Dynamics Using A Coarse-Grained Model, Maneesh Koneru

University Scholar Projects

Though eradicated in most of the world, poliovirus remains a common model virus for a family of mammalian viruses known as Picornaviruses. Despite the development of a vaccination, little is understood about the infection process, particularly the mechanism of cell entry. Experimental studies have attempted to elucidate the dynamics of this process and have proposed pathways focused on VP4, the smallest of the four peptides which makes up the viral capsid, and its interaction with the pentameric interfaces of the five fold axes. This study utilizes coarse-grained molecular dynamics to supplement these proposed mechanisms with simplified simulations which reduce the …

Hard-Sphere-Like Dynamics In Highly Concentrated Alpha-Crystallin Suspensions, Preeti Vodnala, Laurence Lurio, Michael C. Vega, Elizabeth Gaillard

Faculty Peer-Reviewed Publications

The dynamics of concentrated suspensions of the eye-lens protein alpha crystallin have been measured using x-ray photon correlation spectroscopy. Measurements were made at wave vectors corresponding to the first peak in the hard-sphere structure factor and volume fractions close to the critical volume fraction for the glass transition. Langevin dynamics simulations were also performed in parallel to the experiments. The intermediate scattering function f(q,τ) could be fit using a stretched exponential decay for both experiments and numerical simulations. The measured relaxation times show good agreement with simulations for polydisperse hard-sphere colloids.

Transport Of Water And Ions Through Single-Walled Armchair Carbon Nanotubes: A Molecular Dynamics Study, Michelle Patricia Aranha

Doctoral Dissertations

The narrow hydrophobic interior of a carbon nanotube (CNT) poses a barrier to the transport of water and ions, and yet, unexpectedly, numerous experimental and simulation studies have confirmed fast water transport rates comparable to those seen in biological aquaporin channels. These outstanding features of high water permeability and high solute rejection of even dissolved ions that would typically require a lot of energy for separation in commercial processes makes carbon nanotubes an exciting candidate for desalination membranes. Extending ion exclusion beyond simple mechanical sieving by the inclusion of electrostatics via added functionality to the nanotube bears promise to not …

Molecular Mechanisms Of Protein Thermal Stability, Lucas Sawle

Electronic Theses and Dissertations

Organisms that thrive under extreme conditions, such as high salt concentration, low pH, or high temperature, provide an opportunity to investigate the molecular and cellular strategies these organisms have adapted to survive in their harsh environments. Thermophilic proteins, those extracted from organisms that live at high temperature, maintain their structure and function at much higher temperatures compared to their mesophilic counterparts, found in organisms that live near room temperature. Thermophilic and mesophilic homolog protein pairs have identical functionality, and show a high degree of structural and sequential similarity, but differ significantly in their response to high temperature. Addressing the principles …

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 …

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 …

Application Of Computational Molecular Biophysics To Problems In Bacterial Chemotaxis, Davi Ortega

Doctoral Dissertations

The combination of physics, biology, chemistry, and computer science constitutes the promising field of computational molecular biophysics. This field studies the molecular properties of DNA, protein lipids and biomolecules using computational methods. For this dissertation, I approached four problems involving the chemotaxis pathway, the set of proteins that function as the navigation system of bacteria and lower eukaryotes.

In the first chapter, I used a special-purpose machine for molecular dynamics simulations, Anton, to simulate the signaling domain of the chemoreceptor in different signaling states for a total of 6 microseconds. Among other findings, this study provides enough evidence to propose …

Electric Field-Driven Water Dipoles: Nanoscale Architecture Of Electroporation, Mayya Tokman, Jane Hyojin Lee, Zachary A. Levine, Ming-Chak Ho, Michael E. Colvin, P. Thomas Vernier

Bioelectrics Publications

Electroporation is the formation of permeabilizing structures in the cell membrane under the influence of an externally imposed electric field. The resulting increased permeability of the membrane enables a wide range of biological applications, including the delivery of normally excluded substances into cells. While electroporation is used extensively in biology, biotechnology, and medicine, its molecular mechanism is not well understood. This lack of knowledge limits the ability to control and fine-tune the process. In this article we propose a novel molecular mechanism for the electroporation of a lipid bilayer based on energetics analysis. Using molecular dynamics simulations we demonstrate that …

Experimental And Theoretical Investigation Of Molecular Field Effects By Polarization-Resolved Resonant Inelastic X-Ray Scattering, Stephane Carniato, Renaud Guillemin, Wayne C. Stolte, Loic Journel, Richard Taieb, Dennis W. Lindle, Marc Simon

Chemistry and Biochemistry Faculty Research

We present a combined theoretical and experimental study of molecular field effects on molecular core levels. Polarization-dependent resonant inelastic x-ray scattering is observed experimentally after resonant K-shell excitation of CF₃Cl and HCl. We explain the linear dichroism observed in spin-orbit level intensities as due to molecular field effects, including singlet-triplet exchange, and interpret this behavior in terms of population differences in the 2p_x,y,z inner-shell orbitals. We investigate theoretically the different factors that can affect the electronic populations and the dynamical R dependence of the spin-orbit ratio. Finally, the results obtained are used to interpret the L-shell …

Molecular Dynamics Simulations Of Amphiphilic Molecules, Roger L. Mcmullen Jr.

Seton Hall University Dissertations and Theses (ETDs)

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The Spectroscopy And Molecular Dynamics Of The High Frequency Ν1 6 Intermolecular Vibrations In Hcn‐‐‐Hf And Dcn‐‐‐Df, B. A. Wofford, M. W. Jackson, Shannon Lieb, J. W. Bevan

Scholarship and Professional Work - LAS

Gas phase rovibrational analysis of the high frequency intermolecular hydrogen bonded bending overtone 2ν⁰ ₆ [ν₀=1132.4783(2) cm^{− 1}] in HCN‐‐‐HF and its corresponding perdeuterated fundamental ν¹ ₆ [ν₀=409.1660(2) cm^{− 1}] are reported. Evaluated rovibrational parameters provide the basis for quantitative modeling of the molecular dynamics associated with this vibration. A quantum mechanical calculation permits determination of the quadratic and quartic force constants K _{6 6}=537(17) and K _{6 6 6 6}=4.98(12) cm^{− 1} which in turn are used to estimate the pertinent cubic band stretching interaction constants …

Molecular Dynamics In Hydrogen‐Bonded Interactions: A Preliminary Experimentally Determined Harmonic Stretching Force Field For Hcn‐‐‐Hf, B. A. Wofford, Shannon Lieb, J. W. Bevan

Scholarship and Professional Work - LAS

Observation of the 2ν₁ overtone band in the hydrogen‐bonded complex HCN‐‐‐HF permits evaluation of the anharmonicity constant X _{1 1}=−116.9(1) cm^{− 1} and determination of the anharmonicity corrected fundamental frequency ω₁. This information, and available data from previous rovibrational analyses in the common and perdeuterated isotopic species of HCN‐‐‐HF, offer an opportunity for calculation of an approximate stretching harmonic force field. With the assumptions f _{1 2}=f _{2 4}=0.0, the remaining force constants (in mdyn/Å) are evaluated as: f _{1 1}=8.600(20), f _{2 2}=6.228(9), f _{3 3}=19.115(40), f _{4 …}