Application of the Theory of Elasticity to Modeling of Protein -Dna Interactions

88 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2002.A versatile approach to modeling the conformations and energetics of DNA loops is presented. The model is based on the classical theory of elasticity, modified to describe the intrinsic twist and curvature of DNA, the DNA bending anisotropy, and electrostatic properties. All the model parameters are considered to be functions of the loop arclength, so that the DNA sequence-specific properties can be modeled. The developed theory is applied to predict the structure of the DNA loop connecting the protein-bound DNA segments in the crystal structure of the lac repressor-DNA complex. The lac repressor system is used to extensively analyze the parameters and approximations of the model. The capabilities of the model are used to mimic the binding of catabolite gene activator protein (CAP) within the lac repressor loop and to explain the cooperativity in DNA binding between the two proteins. The possibilities for further development of the model and its general applicability in biomolecular modeling are discussed, especially with regard to multi-scale simulations of protein-DNA complexes.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Three Ligands With Biomedical Importance: Binding To Small Zns Quantum Dots

We have performed the first systematic density functional theory study of the coordination of three biomedically significant ligands, acetylcysteine, dihydrolipoic acid, and dopamine, to a small quantum dot (QD), Zn6S6. An exhaustive search for the global minima structures of the ligands and of the ligand-QD species identified several isomers of each compound close in energy to the global minimum structures. The isomeric variety is explained by the presence of several functional groups in the ligands and thus by numerous possibilities of their coordination to the QD. The global minimum structures of the three ligand-QD complexes were further studied with a larger basis set and implicit water effects. The three complexes were shown to be stable, with the anionic ligand species coordinated to the QD being generally more stable than the neutral compounds. The QD distortions because of the coordination with the anionic ligands were much more pronounced than those with the neutral ligands. Charge transfer from both the neutral and anionic ligands to the QD upon the ligand coordination was detected

Three Ligands with Biomedical Importance: Binding to Small ZnS Quantum Dots

We have performed the first systematic density functional theory study of the coordination of three biomedically significant ligands, acetylcysteine, dihydrolipoic acid, and dopamine, to a small quantum dot (QD), Zn₆S₆. An exhaustive search for the global minima structures of the ligands and of the ligand–QD species identified several isomers of each compound close in energy to the global minimum structures. The isomeric variety is explained by the presence of several functional groups in the ligands and thus by numerous possibilities of their coordination to the QD. The global minimum structures of the three ligand–QD complexes were further studied with a larger basis set and implicit water effects. The three complexes were shown to be stable, with the anionic ligand species coordinated to the QD being generally more stable than the neutral compounds. The QD distortions because of the coordination with the anionic ligands were much more pronounced than those with the neutral ligands. Charge transfer from both the neutral and anionic ligands to the QD upon the ligand coordination was detected

Two-Color Spectroscopy Of Uv Excited Ssdna Complex With A Single-Wall Nanotube Photoluminescence Probe: Fast Relaxation By Nucleobase Autoionization Mechanism

DNA autoionization is a fundamental process wherein ultraviolet (UV)-photoexcited nucleobases dissipate energy by charge transfer to the environment without undergoing chemical damage. Here, single-wall carbon nanotubes (SWNT) are explored as a photoluminescent reporter for the study of the mechanism and rates of DNA autoionization. Two-color photoluminescence spectroscopy allows separate photoexcitation of the DNA and the SWNTs in the UV and visible range, respectively. A strong SWNT photoluminescence quenching is observed when the UV pump is resonant with the DNA absorption, consistent with charge transfer from the excited states of the DNA to the SWNT. Semiempirical calculations of the DNA-SWNT electronic structure, combined with a Green’s function theory for charge transfer, show a 20 fs autoionization rate, dominated by hole transfer. Rate-equation analysis of the spectroscopy data confirms that the quenching rate is limited by thermalization of the free charge carriers transferred to the nanotube reservoir. This approach has great potential for monitoring DNA excitation, autoionization, and chemical damage, both in vivo and in vitro. [Figure not available: see fulltext.

Charge Splitters And Charge Transport Junctions Based On Guanine Quadruplexes

Self-assembling circuit elements, such as current splitters or combiners at the molecular scale, require the design of building blocks with three or more terminals. A promising material for such building blocks is DNA, wherein multiple strands can self-assemble into multi-ended junctions, and nucleobase stacks can transport charge over long distances. However, nucleobase stacking is often disrupted at junction points, hindering electric charge transport between the two terminals of the junction. Here, we show that a guanine-quadruplex (G4) motif can be used as a connector element for a multi-ended DNA junction. By attaching specific terminal groups to the motif, we demonstrate that charges can enter the structure from one terminal at one end of a three-way G4 motif, and can exit from one of two terminals at the other end with minimal carrier transport attenuation. Moreover, we study four-way G4 junction structures by performing theoretical calculations to assist in the design and optimization of these connectors