Karl J. Jalkanen

Energetics and structure of glycine and alanine based model peptides: Approximate SCC-DFTB, AM1 and PM3 methods in comparison with DFT, HF and MP2 calculations

We calculate relative energies and geometries of important secondary structural elements for small glycine and alanine based polypeptides containing up to eight residues. We compare the performance of the approximate methods AM1, PM3 and self-consistent charge, density-functional tight-binding (SCC-DFTB) to density-functional theory (DFT), Hartree‐Fock (HF) and MP2. The SCC-DFTB is able to reproduce structures and relative energies of various peptide models reliably compared to DFT results. The AM1 and PM3 methods show deficiencies in describing important secondary structure elements like extended, helical or turn structures. The discrepancies between diAerent ab initio (HF, MP2) and DFT (B3LYP) methods for medium sized basis sets (6-31G*) also show the need for higher level calculations, since systematic errors found for small molecules may add up when investigating longer polypeptides. ” 2001 Elsevier Science B.V. All rights reserved.

The VA and VCD spectra of various isotopomers of l-alanine in aqueous solution

Abstract Density functional theory (DFT) at the Becke 3LYP level has been used to calculate the vibrational absorption (VA) and vibrational circular dichroism (VCD) spectra of various deuterated species of l -alanine. The effect of replacing the methine hydrogen, CH1, the methyl group, CH3, and both the methine and methyl group hydrogens, CH1 and CH3, with the deuteriated species Cd1, Cd3 and Cd1 and Cd3 is investigated, both in H 2 O and D 2 O. The predicted results are then compared to the corresponding experimental spectra. Comparison of the experimental and calculated frequency shifts and intensity changes in the VA and VCD spectra are used as a check of the Becke 3LYP hybrid model to successfully reproduce these fine features in the VA and VCD intensities. Furthermore, several aspects of the isotopomers and the isotope effects on vibrational spectra are discussed in the light of the approximation, i.e., validity of Born–Oppenheimer approximation.

Conformational determination of [Leu]enkephalin based on theoretical and experimental VA and VCD spectral analyses

Conformational determination of [Leu]enkephalin in DMSO-d6 is carried out using VA and VCD spectral analyses. Conformational energies, vibrational frequencies and VA and VCD intensities are calculated using DFT at B3LYP/6-31G* level of theory. Comparison between the measured spectra and the spectral simulations of the low energy conformations of the neutral species enable conformational determination of the molecule. In an earlier study, based only on VA spectroscopy, the results led to the conclusion that [Leu]enkephalin had only a single β-bend conformation of the neutral species in DMSO-d6. The present work shows the importance of using VCD in addition to VA in determining the conformation of chiral molecules and which one of the examined three single β-bend structures is the most stable in DMSO-d6.

ELECTRONIC PATHWAYS IN PHOTOACTIVATED REPAIR OF UV MUTATED DNA

An investigation of the physics, underlying the damage caused to DNA by UV radiation and its subsequent repair via a photoreactivation mechanism, is presented in this study. Electronic pathways, starting from the initial damage to the final repair process, are presented. UV radiation is absorbed to create a hole-excited thymine or other pyrimidine that subsequently is responsible for the formation of a dimer. The negative-ion of the cofactor riboflavin, FADH-, formed by the exposure of the photolyase protein to visible light, interacts with the hole-excited electronic orbital of the thymine dimer inducing a photon-less Auger transition, which restores the two thymines to the ground state, thereby detaching the lesion and repairing the DNA. Density functional theoretical calculations supporting the theory are presented. The mechanism involves the least amount of energy dissipation and is charge neutral. It also avoids radiation damage in the repair process. Recent experimental data are compatible with this theory.

Study of cancer cell lines with Fourier transform infrared (FTIR)/vibrational absorption (VA) spectroscopy

In this work we have used Fourier transform infrared (FTIR) / vibrational absorption (VA) spectroscopy to study two cancer cell lines: the Henrietta Lacks (HeLa) human cervix carcinoma and 5637 human bladder carcinoma cell lines. Our goal is to experimentally investigate biochemical changes and differences in these cells lines utilizing FTIR spectroscopy. We have used the chemometrical and statistical method principal component analysis (PCA) to investigate the spectral differences. We have been able to identify certain bands in the spectra which are so-called biomarkers for two types of cell lines, three groups for the 5637 human bladder carcinoma cell line (5637A, 5637B and 5637C), and another one for the HeLa human cervix carcinoma cell line. The vibrational modes can be assigned to specific bands involving characteristic motions of the protein backbone. This work shows that infrared vibrational absorption (VA) spectroscopy can be used as a useful tool in medical diagnostics that provides in principle additional information and detail to that which can be obtained/provided from conventional histological studies, and more conventional mass spectroscopic and NMR techniques. The use of high level vibrational spectroscopic simulation, in addition to the chemometric and statistical tools of PCA, linear and quadratic discriminant analysis, and artificial networks methods that are good at finding correlations, but provide little if any physical, chemical and biochemical insight into the nature of the changes at a molecular level, is also strongly advocated and helpful to gain more physical, chemical and biological insight. Hence the combination of vibrational spectroscopic simulations and experimental vibrational absorption spectroscopy and imaging are advocated for future developments in this field.

Effects of mannose, fructose, and fucose on the structure, stability, and hydration of lysozyme in aqueous solution

The bio-protective properties of monosaccharaides, namely mannose, fructose and fucose, on the stability and dynamical properties of the NMR determined hen egg-white lysozyme structure have been investigated by means of molecular dynamics simulations at room temperature in aqueous solution and in 7 and 13 wt % concentrations of the three sugars. Results are discussed in the framework of the bio-protective phenomena. The three sugars show similar bio-protective behaviours at room temperature (300 K) in the concentration range studied as shown by the small RMSDs of the resulting MD structures from that of starting NMR structure. The effects of sugars on protein conformation are found to be relatively strong in that the conformation of lysozyme is stable after an initial 9 ns equilibration for fucose and mannose and 12 ns equilibration for fructose, respectively, at high concentrations. For mannose the final RMSD is significantly smaller than that of fucose and fructose at the higher concentration, while at the lower concentration the RMSD are essentially the same. The radial distribution function of the water and sugars around lysozyme was used to monitor the preferential hydration. Analysis of the solvent and sugar distributions around lysozyme was used to investigate the interfacial solvent and sugar structure near the protein surface.

First-principles structures for the close-packed and the 7/2 motif of collagen

The recently proposed close-packed motif for collagen is investigated using first principles semi-empirical wave function theory and Kohn-Sham density functional theory. Under these refinements the close-packed motif is shown to be stable. For the case of the 7/2 motif a similar stability exists. The electronic circular dichroism of the close-packed model has a significant negative bias and a large signal. An interesting feature of the close-packed structure is the existence of a central channel. Simulations show that, if hydrogen atoms are placed in the cavity, a chain of molecular hydrogens is formed suggesting a possible biological function for molecular hydrogen.

On Superconductivity of Matter at High Density and the Effects of Inducing Nuclear Chirality in Molecular Structures

in molecular structures DTU Orbit (11/12/2018) On superconductivity of matter at hight density and the effects of inducing nuclear chirality in molecular structures Superconductivity is described by the well-known Bardeen-Cooper-Schrieffer (BCS) theory, which is a symmetry breaking approximation. Color superconductivity shows up in extremely high density matter and temperature, which is here investigated and compared to the other end of the scale of low energy/temperature of organic superconductors. An approach to color superconductivity conciliating the BCS theory with the color SU(3) symmetry, the cornerstone of the rigorous theory of the strong interaction, Quantum Chromo-Dynamics (QCD), is used to describe the superconducting phase. The magnetization of a high density relativistic fluid of elementary particles is studied. We find that the magnetic field of spin polarized matter with densities of 2 to 30, where 0 is the equilibrium density of nuclear matter, is rather huge, of the order of 1017 Gauss. Finally we look at the chiral nature of nuclear forces and interactions as they possibly relate to chirality of nuclei (atoms) in molecules as a source of chirality in amino acids and hence in life. Previous works have not investigated the nuclear forces as a possible bias which initiated the bias towards L-amino acids as the building blocks on proteins, and later life.