Secondary-Structure Design of Proteins by a Backbone Torsion Energy

We propose a new backbone-torsion-energy term in the force field for protein systems. This torsion-energy term is represented by a double Fourier series in two variables, the backbone dihedral angles phi and psi. It gives a natural representation of the torsion energy in the Ramachandran space in the sense that any two-dimensional energy surface periodic in both phi and psi can be expanded by the double Fourier series. We can then easily control secondary-structure-forming tendencies by modifying the torsion-energy surface. For instance, we can increase/decrease the alpha-helix-forming-tendencies by lowering/raising the torsion-energy surface in the alpha-helix region and likewise increase/decrease the beta-sheet-forming tendencies by lowering/raising the surface in the beta-sheet region in the Ramachandran space. We applied our approach to AMBER parm94 and AMBER parm96 force fields and demonstrated that our modifications of the torsion-energy terms resulted in the expected changes of secondary-structure-forming-tendencies by performing folding simulations of alpha-helical and beta-hairpin peptides.Comment: 13 pages, (Revtex4), 5 figure

Differential Regulation of the Melanoma Proteome by eIF4A1 and eIF4E.

Small molecules and antisense oligonucleotides that inhibit the translation initiation factors eIF4A1 and eIF4E have been explored as broad-based therapeutic agents for cancer treatment, based on the frequent upregulation of these two subunits of the eIF4F cap-binding complex in many cancer cells. Here, we provide support for these therapeutic approaches with mechanistic studies of eIF4F-driven tumor progression in a preclinical model of melanoma. Silencing eIF4A1 or eIF4E decreases melanoma proliferation and invasion. There were common effects on the level of cell-cycle proteins that could explain the antiproliferative effects in vitro Using clinical specimens, we correlate the common cell-cycle targets of eIF4A1 and eIF4E with patient survival. Finally, comparative proteomic and transcriptomic analyses reveal extensive mechanistic divergence in response to eIF4A1 or eIF4E silencing. Current models indicate that eIF4A1 and eIF4E function together through the 5'UTR to increase translation of oncogenes. In contrast, our data demonstrate that the common effects of eIF4A1 and eIF4E on translation are mediated by the coding region and 3'UTR. Moreover, their divergent effects occur through the 5'UTR. Overall, our work shows that it will be important to evaluate subunit-specific inhibitors of eIF4F in different disease contexts to fully understand their anticancer actions. Cancer Res; 77(3); 613-22. ©2016 AACR

Self-Consistent Second Order Perturbation Theory for the Hubbard Model in Two Dimensions

We apply self-consistent second order perturbation theory (SCSOPT) with respect to the on-site repulsive interaction U to study the Hubbard model in two dimensions. We investigate single particle properties of the model over the entire doping range at zero temperature. It is shown that as doping decreases toward half-filling $\omega$-mass enhancement factor increases, while k-mass enhancement factor decreases. The increase in $\omega$-mass enhancement factor is larger than the decrease in k-mass enhancement factor, so that total-mass is larger than that in the non-interacting case. When particle number density per unit cell n is given by 0.64<n<1.0 interaction enhances anisotropy of the Fermi surface, whereas at lower densities n<0.64 interaction suppresses anisotropy of it. Due to the decrease in k-mass enhancement factor the density of states (DOS) at the Fermi level is suppressed. It is possible to understand the results within the framework of the weak coupling Fermi liquid theory.Comment: 8 pages, 12 embedded EPS figures, to appear in J. Phys. Soc. Jpn. Vol. 68-3 (1999

Characterization of a synthetic peroxodiiron(III) protein model complex by nuclear resonance vibrational spectroscopy

The vibrational spectrum of an η[superscript 1],η[superscript 1]-1,2-peroxodiiron(III) complex was measured by nuclear resonance vibrational spectroscopy and fit using an empirical force field analysis. Isotopic 18O2 labelling studies revealed a feature involving motion of the {Fe2(O2)}[superscript 4+] core that was not previously observed by resonance Raman spectroscopy.National Institute of General Medical Sciences (U.S.) (GM-032134

Electronic and Magnetic Phase Diagram of a Superconductor, SmFeAsO1-xFx

A crystallographic and magnetic phase diagram of SmFeAsO1-xFx is determined as a function of x in terms of temperature based on electrical transport and magnetization, synchrotron powder x-ray diffraction, 57Fe Mossbauer spectra (MS), and 149Sm nuclear resonant forward scattering (NRFS) measurements. MS revealed that the magnetic moments of Fe were aligned antiferromagnetically at ~144 K (TN(Fe)). The magnetic moment of Fe (MFe) is estimated to be 0.34 myuB/Fe at 4.2 K for undoped SmFeAsO; MFe is quenched in superconducting F-doped SmFeAsO. 149Sm NRFS spectra revealed that the magnetic moments of Sm start to order antiferromagnetically at 5.6 K (undoped) and 4.4 K (TN(Sm)) (x = 0.069). Results clearly indicate that the antiferromagnetic Sm sublattice coexists with the superconducting phase in SmFeAsO1-xFx below TN(Sm), while antiferromagnetic Fe sublattice does not coexist with the superconducting phase.Comment: Accepted in New Journal of Physic

Co-localization of CENP-C and CENP-H to discontinuous domains of CENP-A chromatin at human neocentromeres

The distribution of centromeric chromatin-associated proteins across human neocentromeric DNA shows that this chromatin consists of several CENP-A-containing sub-domains

Interaction induced collapse of a section of the Fermi sea in in the zig-zag Hubbard ladder

Using the next-nearest neighbor (zig-zag) Hubbard chain as an one dimemensional model, we investigate the influence of interactions on the position of the Fermi wavevectors with the density-matrix renormalization-group technique (DMRG). For suitable choices of the hopping parameters we observe that electron-electron correlations induce very different renormalizations for the two different Fermi wavevectors, which ultimately lead to a complete destruction of one section of the Fermi sea in a quantum critical point

Nitrosylation of Nitric-Oxide-Sensing Regulatory Proteins Containing [4Fe-4S] Clusters Gives Rise to Multiple Iron-Nitrosyl Complexes

The reaction of protein-bound iron–sulfur (Fe-S) clusters with nitric oxide (NO) plays key roles in NO-mediated toxicity and signaling. Elucidation of the mechanism of the reaction of NO with DNA regulatory proteins that contain Fe-S clusters has been hampered by a lack of information about the nature of the iron-nitrosyl products formed. Herein, we report nuclear resonance vibrational spectroscopy (NRVS) and density functional theory (DFT) calculations that identify NO reaction products in WhiD and NsrR, regulatory proteins that use a [4Fe-4S] cluster to sense NO. This work reveals that nitrosylation yields multiple products structurally related to Roussin's Red Ester (RRE, [Fe2(NO)4(Cys)2]) and Roussin's Black Salt (RBS, [Fe4(NO)7S3]. In the latter case, the absence of 32S/34S shifts in the Fe−S region of the NRVS spectra suggest that a new species, Roussin's Black Ester (RBE), may be formed, in which one or more of the sulfide ligands is replaced by Cys thiolates

Spin-boson models for quantum decoherence of electronic excitations of biomolecules and quantum dots in a solvent

We give a theoretical treatment of the interaction of electronic excitations (excitons) in biomolecules and quantum dots with the surrounding polar solvent. Significant quantum decoherence occurs due to the interaction of the electric dipole moment of the solute with the fluctuating electric dipole moments of the individual molecules in the solvent. We introduce spin boson models which could be used to describe the effects of decoherence on the quantum dynamics of biomolecules which undergo light-induced conformational change and on biomolecules or quantum dots which are coupled by Forster resonant energy transfer.Comment: More extended version, to appear in Journal of Physics: Condensed Matter. 13 pages, 3 figure