When fragments link : a bibliometric perspective on the development of fragment-based drug discovery

Fragment-based drug discovery (FBDD) is a highly interdisciplinary field, rich in ideas integrated from pharmaceutical sciences, chemistry, biology, and physics, among others. To enrich our understanding of the development of the field, we used bibliometric techniques to analyze 3642 publications in FBDD, complementing accounts by key practitioners. Mapping its core papers, we found the transfer of knowledge from academia to industry. Co-authorship analysis showed that university–industry collaboration has grown over time. Moreover, we show how ideas from other scientific disciplines have been integrated into the FBDD paradigm. Keyword analysis showed that the field is organized into four interconnected practices: library design, fragment screening, computational methods, and optimization. This study highlights the importance of interactions among various individuals and institutions from diverse disciplines in newly emerging scientific fields. We study the organizational aspects of the development of fragment-based drug discovery (FBDD), using tools from bibliometrics

Electronic structure, phase stability and chemical bonding in Th2_2Al and Th2_2AlH4_4

We present the results of theoretical investigation on the electronic structure, bonding nature and ground state properties of Th$_2$Al and Th$_2$AlH$_4$ using generalized-gradient-corrected first-principles full-potential density-functional calculations. Th$_2$AlH$_4$ has been reported to violate the "2 \AA rule" of H-H separation in hydrides. From our total energy as well as force-minimization calculations, we found a shortest H-H separation of 1.95 {\AA} in accordance with recent high resolution powder neutron diffraction experiments. When the Th$_2$Al matrix is hydrogenated, the volume expansion is highly anisotropic, which is quite opposite to other hydrides having the same crystal structure. The bonding nature of these materials are analyzed from the density of states, crystal-orbital Hamiltonian population and valence-charge-density analyses. Our calculation predicts different nature of bonding for the H atoms along $a$ and $c$. The strongest bonding in Th$_2$AlH$_4$ is between Th and H along $c$ which form dumb-bell shaped H-Th-H subunits. Due to this strong covalent interaction there is very small amount of electrons present between H atoms along $c$ which makes repulsive interaction between the H atoms smaller and this is the precise reason why the 2 {\AA} rule is violated. The large difference in the interatomic distances between the interstitial region where one can accommodate H in the $ac$ and $ab$ planes along with the strong covalent interaction between Th and H are the main reasons for highly anisotropic volume expansion on hydrogenation of Th$_2$Al.Comment: 14 pages, 9 figure

Charge and spin order in one-dimensional electron systems with long-range Coulomb interactions

We study a system of electrons interacting through long--range Coulomb forces on a one--dimensional lattice, by means of a variational ansatz which is the strong--coupling counterpart of the Gutzwiller wave function. Our aim is to describe the quantum analogue of Hubbard's classical ``generalized Wigner crystal''. We first analyse charge ordering in a system of spinless fermions, with particular attention to the effects of lattice commensurability. We argue that for a general (rational) number of electrons per site $n$ there are three regimes, depending on the relative strength $V$ of the long--range Coulomb interaction (as compared to the hopping amplitude $t$). For very large $V$ the quantum ground state differs little from Hubbard's classical solution, for intermediate to large values of $V$ we recover essentially the Wigner crystal of the continuum model, and for small $V$ the charge modulation amounts to a small--amplitude charge--density wave. We then include the spin degrees of freedom and show that in the Wigner crystal regimes (i.e. for large $V$) they are coupled by an antiferromagnetic kinetic exchange $J$, which turns out to be smaller than the energy scale governing the charge degrees of freedom. Our results shed new light on the insulating phases of organic quasi--1D compounds where the long--range part of the interaction is unscreened, and magnetic and charge orderings coexist at low temperatures.Comment: 11 pages, 7 figures, accepted for publication on Phys. Rev.

Modeling the actinides with disordered local moments

A first-principles disordered local moment (DLM) picture within the local-spin-density and coherent potential approximations (LSDA+CPA) of the actinides is presented. The parameter free theory gives an accurate description of bond lengths and bulk modulus. The case of $\delta$-Pu is studied in particular and the calculated density of states is compared to data from photo-electron spectroscopy. The relation between the DLM description, the dynamical mean field approach and spin-polarized magnetically ordered modeling is discussed.Comment: 6 pages, 4 figure

Electronic structure of the quasi-one-dimensional organic conductor TTF-TCNQ

We study the electronic structure of the quasi-one-dimensional organic conductor TTF-TCNQ by means of density-functional band theory, Hubbard model calculations, and angle-resolved photoelectron spectroscopy (ARPES). The experimental spectra reveal significant quantitative and qualitative discrepancies to band theory. We demonstrate that the dispersive behavior as well as the temperature-dependence of the spectra can be consistently explained by the finite-energy physics of the one-dimensional Hubbard model at metallic doping. The model description can even be made quantitative, if one accounts for an enhanced hopping integral at the surface, most likely caused by a relaxation of the topmost molecular layer. Within this interpretation the ARPES data provide spectroscopic evidence for the existence of spin-charge separation on an energy scale of the conduction band width. The failure of the one-dimensional Hubbard model for the {\it low-energy} spectral behavior is attributed to interchain coupling and the additional effect of electron-phonon interaction.Comment: 18 pages, 9 figure

Poor screening and nonadiabatic superconductivity in correlated systems

In this paper we investigate the role of the electronic correlation on the hole doping dependence of electron-phonon and superconducting properties of cuprates. We introduce a simple analytical expression for the one-particle Green's function in the presence of electronic correlation and we evaluate the reduction of the screening properties as the electronic correlation increases by approaching half-filling. The poor screening properties play an important role within the context of the nonadiabatic theory of superconductivity. We show that a consistent inclusion of the reduced screening properties in the nonadiabatic theory can account in a natural way for the $T_c$-$\delta$ phase diagram of cuprates. Experimental evidences are also discussed.Comment: 12 Pages, 6 Figures, Accepted on Physical Review

Universality, the QCD critical/tricritical point and the quark number susceptibility

The quark number susceptibility near the QCD critical end-point (CEP), the tricritical point (TCP) and the O(4) critical line at finite temperature and quark chemical potential is investigated. Based on the universality argument and numerical model calculations we propose a possibility that the hidden tricritical point strongly affects the critical phenomena around the critical end-point. We made a semi-quantitative study of the quark number susceptibility near CEP/TCP for several quark masses on the basis of the Cornwall-Jackiw-Tomboulis (CJT) potential for QCD in the improved-ladder approximation. The results show that the susceptibility is enhanced in a wide region around CEP inside which the critical exponent gradually changes from that of CEP to that of TCP, indicating a crossover of different universality classes.Comment: 18 pages, 10 figure

Local field factors in a polarized two-dimensional electron gas

We derive approximate expressions for the static local field factors of a spin polarized two-dimensional electron gas which smoothly interpolate between their small- and large-wavevector asymptotic limits. For the unpolarized electron gas, the proposed analytical expressions reproduce recent diffusion Monte Carlo data. We find that the degree of spin polarization produces important modifications to the local factors of the minority spins, while the local field functions of the majority spins are less affected.Comment: 8 pages, 10 figure

The degenerate 3-band Hubbard model with "anti-Hund's rule" interactions; a model for AxC60

We consider the orbitally degenerate 3-band Hubbard model with on-site interactions which favor low spin and low orbital angular momentum using standard second order perturbation theory in the large Hubbard-U limit. At even integer filling this model is a Mott insulator with a non-degenerate ground state that allows for a simple description of particle-hole excitations as well as gapped spin and orbital modes. We find that the Mott gap is generally indirect and that the single particle spectrum at low doping reappears close to even filling but rescaled by a factor 2/3 or 1/3. The model captures the basic phenomenology of the Mott insulating and metallic fullerides AxC60. This includes the existence of a smaller spin gap and larger charge gap at even integer filling, the fact that odd integer stoichiometries are generally metallic while even are insulating, as well as the rapid suppression of the density of states and superconducting transition temperatures with doping away from x=3.Comment: Revised with additional reference

Statistical Theory of Spin Relaxation and Diffusion in Solids

A comprehensive theoretical description is given for the spin relaxation and diffusion in solids. The formulation is made in a general statistical-mechanical way. The method of the nonequilibrium statistical operator (NSO) developed by D. N. Zubarev is employed to analyze a relaxation dynamics of a spin subsystem. Perturbation of this subsystem in solids may produce a nonequilibrium state which is then relaxed to an equilibrium state due to the interaction between the particles or with a thermal bath (lattice). The generalized kinetic equations were derived previously for a system weakly coupled to a thermal bath to elucidate the nature of transport and relaxation processes. In this paper, these results are used to describe the relaxation and diffusion of nuclear spins in solids. The aim is to formulate a successive and coherent microscopic description of the nuclear magnetic relaxation and diffusion in solids. The nuclear spin-lattice relaxation is considered and the Gorter relation is derived. As an example, a theory of spin diffusion of the nuclear magnetic moment in dilute alloys (like Cu-Mn) is developed. It is shown that due to the dipolar interaction between host nuclear spins and impurity spins, a nonuniform distribution in the host nuclear spin system will occur and consequently the macroscopic relaxation time will be strongly determined by the spin diffusion. The explicit expressions for the relaxation time in certain physically relevant cases are given.Comment: 41 pages, 119 Refs. Corrected typos, added reference