Warm and Cold Denaturation in the Phase Diagram of a Protein Lattice Model

Studying the properties of the solvent around proteins, we propose a much more sophisticated model of solvation than temperature-independent pairwise interactions between monomers, as is used commonly in lattice representations. We applied our model of solvation to a 16-monomer chain constrained on a two-dimensional lattice. We compute a phase diagram function of the temperature and a solvent parameter which is related to the pH of the solution. It exhibits a native state in which the chain coalesces into a unique compact conformation as well as a denatured state. Under certain solvation conditions, both warm and cold denaturations occur between the native and the denatured states. A good agreement is found with the data obtained from calorimetric experiments, thereby validating the proposed model.Comment: 7 pages, 2 figure

Solvent Effects on Ionization Potentials of Guanine Runs and Chemically Modified Guanine in Duplex DNA: Effect of Electrostatic Interaction and Its Reduction due to Solvent

We examined the ionization potential (IP) corresponding to the free energy of a hole on duplex DNA by semiempirical molecular orbital theory with a continuum solvent model. As for the contiguous guanines (a guanine run), we found that the IP in the gas phase significantly decreases with the increasing number of nucleotide pairs of the guanine run, whereas the IP in water (OP, oxidation potential) only slightly does. The latter result is consistent with the experimental result for DNA oligomers in water. This decrease in the IP is mainly due to the attractive electrostatic interaction between the hole and a nucleotide pair in the duplex DNA. This interaction is reduced in water, which results in the small decrease in the IP in water. This mechanism explains the discrepancy between the experimental result and the previous computational results obtained by neglecting the solvent. As for the chemically modified guanine, the previous work showed that the removal of some solvent (water) molecules due to the attachment of a neutral functional group to a guanine in a duplex DNA stabilizes the hole on the guanine. One might naively have expected the opposite case, since a polar solvent usually stabilizes ions. This mechanism also explains this unexpected stabilization of a hole as follows. When some water molecules are removed, the attractive electrostatic interaction stabilizing the hole increases, and thus, the hole is stabilized. In order to design the hole energetics by a chemical modification of DNA, this mechanism has to be taken into account and can be used. 1

Assembly and structural analysis of a covalently closed nano-scale DNA cage

The inherent properties of DNA as a stable polymer with unique affinity for partner molecules determined by the specific Watson–Crick base pairing makes it an ideal component in self-assembling structures. This has been exploited for decades in the design of a variety of artificial substrates for investigations of DNA-interacting enzymes. More recently, strategies for synthesis of more complex two-dimensional (2D) and 3D DNA structures have emerged. However, the building of such structures is still in progress and more experiences from different research groups and different fields of expertise are necessary before complex DNA structures can be routinely designed for the use in basal science and/or biotechnology. Here we present the design, construction and structural analysis of a covalently closed and stable 3D DNA structure with the connectivity of an octahedron, as defined by the double-stranded DNA helices that assembles from eight oligonucleotides with a yield of ∼30%. As demonstrated by Small Angle X-ray Scattering and cryo-Transmission Electron Microscopy analyses the eight-stranded DNA structure has a central cavity larger than the apertures in the surrounding DNA lattice and can be described as a nano-scale DNA cage, Hence, in theory it could hold proteins or other bio-molecules to enable their investigation in certain harmful environments or even allow their organization into higher order structures

Hydration effects in a lattice model of protein folding

The problem of protein folding is approached by introducing explicit solvent effects on a lattice model of chains composed of hydrophobic and polar units. The free energy and entropy of the chain hydration are defined using different values for the contact energy between units. Results obtained from an exhaustive exploration, on a 2D lattice, of the complete set of conformations and possible sequences of 10 unit chains, show that hydration decreases the degeneracy of the ground state of certain sequences, thus allowing a better selection between the specific sequences which present a low free energy and compact structures

A critical analysis of a left-handed double helix model for B-DNA fibers.

A search for a left-handed double helix model for B-DNA fibers has been undertaken. The model has to present good stereochemistry and also to be in agreement with X-ray and infrared data. Dihedral angles as well as atomic coordinates and calculated intensities curves are given for the best model obtained. Comparison with experimental results shows that this model must be rejected as a candidate for the representation of B-DNA fibers

Computational aspects of the three-dimensional feature-scale simulation of silicon-nanowire field-effect sensors for DNA detection

In recent years DNA-sensors, and generally biosensors, with semiconducting transducers were fabricated and characterized. Although the concept of so-called BioFETs was proposed already two decades ago, its realization has become feasible only recently due to advances in process technology. In this paper a comprehensive and rigorous approach to the simulation of silicon-nanowire DNAFETs at the feature-scale is presented. It allows to investigate the feasibility of single-molecule detectors and is used to elucidate the performance that can be expected from sensors with nanowire diameters in the deca-nanometer range. Finally the computational challenges for the simulation of silicon-nanowire DNA-sensors are discussed