Biomedical subjects

Poul Jørgensen

Publications and source records attributed to Poul Jørgensen.

14 recordsLinked to original sources

PubMed2006

The equilibrium structure of ferrocene.

The molecular structures of ferrocene in the eclipsed (equilibrium) and staggered (saddle-point) conformations have been determined by full geometry optimizations at the levels of second-order Møller-Plesset (MP2) theory, coupled-cluster singles-and-doubles (CCSD) theory, and CCSD theory with a perturbative triples correction [CCSD(T)] in a TZV2P+f basis set. Existing experimental results are reviewed. The agreement between the CCSD(T) results and experiment is in all cases excellent; the calculated structure parameters and the barrier to internal rotation of the ligand rings differ from the most accurate experimental values by less than two estimated standard deviations. The CCSD(T) calculations for single-configuration-dominated transition metal complexes such as ferrocene thus appear to have an accuracy comparable to that observed for molecules containing only first- and second-row atoms, and to be of a quality similar to that obtained experimentally. A comparison with previous DFT results indicates that the B3LYP model gives overall the best DFT results, with a deviation of around 2 pm for the metal-carbon distance and smaller errors for the cyclopentadienyl rings.

Journal Article↗

PubMed2005

Quadratic response functions in a second-order polarization propagator framework.

The linear and quadratic response functions have been derived for an exact state, based on an exponential parametrization of the time evolution consisting of products of exponentials for orbital rotations and for higher-order excitations. Truncating the linear response function such that the response function itself and its pole structure is correct to second order in Møller-Plesset perturbation theory, we arrive at the second-order polarization propagator approximation (SOPPA). Previous derivations of SOPPA have used the superoperator formalism, making the extension of SOPPA to quadratic and higher order response functions difficult. The derivation of the quadratic response function is described in detail, allowing molecular properties such as hyperpolarizabilities, two-photon cross sections, and excited-state properties to be calculated using the SOPPA model.

Journal Article↗

PubMed2005

Weak intramolecular interactions in ethylene glycol identified by vapor phase OH-stretching overtone spectroscopy.

Vapor phase OH-stretching overtone spectra of ethylene glycol were recorded to investigate weak intramolecular hydrogen bonding. The spectra were recorded with conventional absorption spectroscopy and laser photoacoustic spectroscopy in the first to fourth OH-stretching overtone regions. The room-temperature spectra are dominated by two conformers that show weak intramolecular hydrogen bonding. A less abundant third conformer, with no sign of hydrogen bonding, is also observed. Vapor phase spectra of the ethylene-d(4) glycol isotopomer were also recorded and used to identify an interfering resonance between CH-stretching and OH-stretching states in the fourth overtone. Anharmonic oscillator local mode calculations of the OH-stretching transitions have provided an accurate simulation of the observed spectra. The local mode parameters were calculated with coupled cluster ab initio methods. The calculations facilitate assignment of the different conformers in the spectra and illustrate the effect of the intramolecular hydrogen bonding.

Journal Article↗

PubMed2005

The accuracy of ab initio molecular geometries for systems containing second-row atoms.

The performance of the standard hierarchy of ab initio models--that is, Hartree-Fock theory, second-order Moller-Plesset theory, coupled-cluster singles-and-doubles theory, and coupled-cluster singles-doubles-approximate-triples theory--in combination with correlation-consistent basis sets is investigated for equilibrium geometries of molecules containing second-row elements. From an analysis on a collection of 31 molecules (yielding statistical samples of 41 bond distances and 13 bond angles), the statistical errors (mean deviation, mean absolute deviation, standard deviation, and maximum absolute deviation) are established at each level of theory. The importance of core correlation is examined by comparing calculations in the frozen-core approximation with calculations where all electrons are correlated.

Journal Article↗

PubMed2005

The trust-region self-consistent field method in Kohn-Sham density-functional theory.

The trust-region self-consistent field (TRSCF) method is extended to the optimization of the Kohn-Sham energy. In the TRSCF method, both the Roothaan-Hall step and the density-subspace minimization step are replaced by trust-region optimizations of local approximations to the Kohn-Sham energy, leading to a controlled, monotonic convergence towards the optimized energy. Previously the TRSCF method has been developed for optimization of the Hartree-Fock energy, which is a simple quadratic function in the density matrix. However, since the Kohn-Sham energy is a nonquadratic function of the density matrix, the local energy functions must be generalized for use with the Kohn-Sham model. Such a generalization, which contains the Hartree-Fock model as a special case, is presented here. For comparison, a rederivation of the popular direct inversion in the iterative subspace (DIIS) algorithm is performed, demonstrating that the DIIS method may be viewed as a quasi-Newton method, explaining its fast local convergence. In the global region the convergence behavior of DIIS is less predictable. The related energy DIIS technique is also discussed and shown to be inappropriate for the optimization of the Kohn-Sham energy.

Algorithms↗

PubMed2004

The Cotton-Mouton effect of neon and argon: a benchmark study using highly correlated coupled cluster wave functions.

The Cotton-Mouton effect (magnetic field induced linear birefringence) has been studied for neon and argon using state-of-the-art coupled cluster techniques. The coupled cluster singles, doubles and triples (CCSDT) approach has been used to obtain static benchmark results and the CC3 model with an approximate treatment of triple excitations to obtain frequency-dependent results. In the case of neon the effect of excitations beyond triples has also been estimated via coupled cluster calculations including quadruple excitations (CCSDTQ), pentuple excitations (CCSDTQP), etc. up to the full configuration-interaction level. The results obtained for the anisotropy of the hypermagnetizability Deltaeta(omega), the molecular property that determines the magnetic field induced birefringence of spherically symmetric systems, are Deltaeta=2.89 a.u. for neon and Deltaeta=24.7 a.u. for argon, with a negligible effect of frequency dispersion. For neon we could estimate an absolute error on Deltaeta of 0.1 a.u. The accuracy of these results surpasses that of recently reported experimental data.

Journal Article↗

PubMed2004

A closed-shell coupled-cluster treatment of the Breit-Pauli first-order relativistic energy correction.

First-order relativistic corrections to the energy of closed-shell molecular systems are calculated, using all terms in the two-component Breit-Pauli Hamiltonian. In particular, we present the first implementation of the two-electron Breit orbit-orbit integrals, thus completing the first-order relativistic corrections within the two-component Pauli approximation. Calculations of these corrections are presented for a series of small and light molecules, at the Hartree-Fock and coupled-cluster levels of theory. Comparisons with four-component Dirac-Coulomb-Breit calculations demonstrate that the full Breit-Pauli energy corrections represent an accurate approximation to a fully relativistic treatment of such systems. The Breit interaction is dominated by the spin-spin interaction, the orbit-orbit interaction contributing only about 10% to the total two-electron relativistic correction in molecules consisting of light atoms. However, the relative importance of the orbit-orbit interaction increases with increasing nuclear charge, contributing more than 20% in H(2)S.

Journal Article↗

PubMed2004

Coupled-cluster connected quadruples and quintuples corrections to the harmonic vibrational frequencies and equilibrium bond distances of HF, N(2), F(2), and CO.

Using the coupled-cluster method, we have examined the contributions from the connected quadruple and quintuple virtual excitations to the harmonic vibrational frequencies and equilibrium bond distances of HF, N(2), F(2), and CO. Whereas the largest quadruples contributions are -18.8 cm(-1) to the harmonic frequency of N(2) and 0.43 pm to the bond distance of F(2), the largest quintuples contributions are -3.9 cm(-1) to the harmonic frequency of N(2) and 0.03 pm to the bond distances of N(2) and F(2). As we improve the description by going from the coupled-cluster singles-and-doubles model with a perturbative triples correction [CCSD(T)] to the coupled-cluster singles-doubles-triples-and-quadruples model, the mean and maximum absolute errors in the calculated frequencies relative to experiment are reduced from 11.3 and 15.8 cm(-1), respectively, to 3.2 and 4.7 cm(-1); for the bond distances, the mean and maximum absolute errors are reduced from 0.16 and 0.47 pm, respectively, to 0.04 and 0.13 pm. The calculations presented here confirm previous observations that, to some extent, the relatively small errors in the CCSD(T) equilibrium bond distances and harmonic frequencies arise from a cancellation of errors in the approximate (perturbative) treatment of the connected triples and the neglect of higher-order connected excitations. Further inclusion of quintuples contributions, relativistic corrections, and adiabatic corrections reduces the mean and maximum absolute errors to 1.1 and 2.3 cm(-1), respectively, for the harmonic frequencies and to 0.02 and 0.05 pm, respectively, for the bond distances.

Journal Article↗

PubMed2004

The trust-region self-consistent field method: towards a black-box optimization in Hartree-Fock and Kohn-Sham theories.

The trust-region self-consistent field (TRSCF) method is presented for optimizing the total energy E(SCF) of Hartree-Fock theory and Kohn-Sham density-functional theory. In the TRSCF method, both the Fock/Kohn-Sham matrix diagonalization step to obtain a new density matrix and the step to determine the optimal density matrix in the subspace of the density matrices of the preceding diagonalization steps have been improved. The improvements follow from the recognition that local models to E(SCF) may be introduced by carrying out a Taylor expansion of the energy about the current density matrix. At the point of expansion, the local models have the same gradient as E(SCF) but only an approximate Hessian. The local models are therefore valid only in a restricted region-the trust region-and steps can only be taken with confidence within this region. By restricting the steps of the TRSCF model to be inside the trust region, a monotonic and significant reduction of the total energy is ensured in each iteration of the TRSCF method. Examples are given where the TRSCF method converges monotonically and smoothly, but where the standard DIIS method diverges.

Journal Article↗

PubMed2004

Nizp1, a novel multitype zinc finger protein that interacts with the NSD1 histone lysine methyltransferase through a unique C2HR motif.

Haploinsufficiency of the NSD1 gene is a hallmark of Sotos syndrome, and rearrangements of this gene by translocation can cause acute myeloid leukemia. The NSD1 gene product is a SET-domain histone lysine methyltransferase that has previously been shown to interact with nuclear receptors. We describe here a novel NSD1-interacting protein, Nizp1, that contains a SCAN box, a KRAB-A domain, and four consensus C2H2-type zinc fingers preceded by a unique finger derivative, referred to herein as the C2HR motif. The C2HR motif functions to mediate protein-protein interaction with the cysteine-rich (C5HCH) domain of NSD1 in a Zn(II)-dependent fashion, and when tethered to RNA polymerase II promoters, represses transcription in an NSD1-dependent manner. Mutations of the cysteine or histidine residues in the C2HR motif abolish the interaction of Nizp1 with NSD1 and compromise the ability of Nizp1 to repress transcription. Interestingly, converting the C2HR motif into a canonical C2H2 zinc finger has a similar effect. Thus, Nizp1 contains a novel type of zinc finger motif that functions as a docking site for NSD1 and is more than just a degenerate evolutionary remnant of a C2H2 motif.

Amino Acid Motifs↗

PubMed2003

The acetyltransferase 60 kDa trans-acting regulatory protein of HIV type 1-interacting protein (Tip60) interacts with the translocation E26 transforming-specific leukaemia gene (TEL) and functions as a transcriptional co-repressor.

The translocation E26 transforming-specific (ETS) leukaemia (TEL), alias the ETS variant (ETV6), gene is expressed in most human tissues and encodes a transcriptional repressor. The TEL gene is involved in more than 40 different chromosomal translocations associated with haematological malignancies. As little is known about the function of intact TEL, we searched for TEL-interacting proteins by yeast two-hybrid screening. Among the interacting partners, we identified the histone acetyltransferase protein Tip60 [60 kDa trans-acting regulatory protein of HIV type 1 (Tat)-interacting protein]. The interaction was reproduced in vitro, and in mammalian cells we mapped the interaction regions in TEL to the ETS domain and those in Tip60 to the MYST ('MOZ, Ybf2/Sas3, SAS2 and Tip60', where MOZ stands for male absent on the first, SAS for something about silencing and Ybf2 for identical with SAS2) region. Detailed analysis of the Tip60 MYST domain by introduction of point mutations revealed that an N-terminal C2HC zinc finger was essential for interaction with TEL. Finally, we showed that Tip60 functions in a reporter system as a co-repressor in TEL-mediated transcription repression.

Acetylation↗

PubMed2002

A new splice variant of glial fibrillary acidic protein, GFAP epsilon, interacts with the presenilin proteins.

We describe a new human isoform, GFAP epsilon, of the intermediary filament protein GFAP (glial fibrillary acidic protein). GFAP epsilon mRNA is the result of alternative splicing and a new polyadenylation signal, and thus GFAP epsilon has a new C-terminal protein sequence. This provides GFAP epsilon with the capacity for specific binding of presenilin proteins in yeast and in vitro. Our observations suggest a direct link between the presenilins and the cytoskeleton where GFAP epsilon is incorporated. Mutations in GFAP and presenilins are associated with Alexander disease and Alzheimer's disease, respectively. Accordingly, GFAP epsilon should be taken into consideration when studying neurodegenerative diseases.

Alternative Splicing↗

PubMed2002

Neurobehavioral performance of Inuit children with increased prenatal exposure to methylmercury.

Exposure to methylmercury from marine mammals and other seafood may affect the development of the central nervous system. In a traditional Inuit community in Qaanaaq, Greenland, mercury concentrations in cord blood and maternal hair have been examined in connection with all births. We examined 43 children at age 7-12 years with a battery of neurobehavioral tests. The average mercury concentration in hair was 5.0 microg/g and 1.5 microg/g in children and mothers, respectively. Clinical neurological examination did not reveal any obvious deficits. However, neuropsychological tests showed possible exposure-associated deficits, though only in a few cases reaching statistical significance. In conjunction with data from other studies, peak latencies on brainstem auditory evoked potentials tended to be prolonged at increased exposure levels. The data from the present study therefore appears in accordance with other evidence that prenatal or early postnatal exposures to methylmercury may cause subtle neurobehavioral deficits.

Brain Stem↗

PubMedDate not supplied

Mutations associated with a childhood leukodystrophy, Alexander disease, cause deficiency in dimerization of the cytoskeletal protein GFAP.

Heterozygous, de novo mutations in the glial fibrillary acidic protein (GFAP) gene were recently found to be associated with Alexander disease. We examined the functional effect of such mutations, and observed a decrease in GFAP dimerization. This effect behaves in a dominant fashion and points towards a potential mechanism in pathogenesis.

Alexander Disease↗