Chemical Space Exploration with Active Learning and Alchemical Free Energies

Drug discovery can be thought of as a search for a needle in a haystack: searching through a large chemical space for the most active compounds. Computational techniques can narrow the search space for experimental follow up, but even they become unaffordable when evaluating large numbers of molecules. Therefore, machine learning (ML) strategies are being developed as computationally cheaper complementary techniques for navigating and triaging large chemical libraries. Here, we explore how an active learning protocol can be combined with first-principles based alchemical free energy calculations to identify high affinity phosphodiesterase 2 (PDE2) inhibitors. We first calibrate the procedure using a set of experimentally characterized PDE2 binders. The optimized protocol is then used prospectively on a large chemical library to navigate toward potent inhibitors. In the active learning cycle, at every iteration a small fraction of compounds is probed by alchemical calculations and the obtained affinities are used to train ML models. With successive rounds, high affinity binders are identified by explicitly evaluating only a small subset of compounds in a large chemical library, thus providing an efficient protocol that robustly identifies a large fraction of true positives

Influence of Magnetism on Phonons in CaFe2As2 Via Inelastic X-ray Scattering

In the iron pnictides, the strong sensitivity of the iron magnetic moment to the arsenic position suggests a significant relationship between phonons and magnetism. We measured the phonon dispersion of several branches in the high temperature tetragonal phase of CaFe2As2 using inelastic x-ray scattering on single-crystal samples. These measurements were compared to ab initio calculations of the phonons. Spin polarized calculations imposing the antiferromagnetic order present in the low temperature orthorhombic phase dramatically improve agreement between theory and experiment. This is discussed in terms of the strong antiferromagnetic correlations that are known to persist in the tetragonal phase.Comment: 4 pages, 3 figures; added additional information and references about spin fluctuation

First-principles study of the optoelectronic properties and photovoltaic absorber layer efficiency of Cu-based chalcogenides

Cu-based chalcogenides are promising materials for thin-film solar cells with more than 20% measured cell efficiency. Using first-principles calculations based on density functional theory, the optoelectronic properties of a group of Cu-based chalcogenides Cu$_2$-II-IV-VI$_4$ is studied. They are then screened with the aim of identifying potential absorber materials for photovoltaic applications. The spectroscopic limited maximum efficiency (SLME) introduced by Yu and Zunger is used as a metric for the screening. After constructing the current-voltage curve, the maximum spectroscopy dependent power conversion efficiency is calculated from the maximum power output. The role of the nature of the band gap, direct or indirect, and also of the absorptivity of the studied materials on the maximum theoretical power conversion efficiency is studied. Our results show that Cu$_2$-II-GeSe$_4$ with II=Cd and Hg, and Cu$_2$-II-SnS$_4$ with II=Cd and Zn have a higher theoretical efficiency compared to the materials currently used as absorber layer

Dinuclear Tb and Dy complexes supported by hybrid Schiff-base/calixarene ligands: synthesis, structures and magnetic properties

The synthesis of the new lanthanide complexes [HNEt$_{3}$][Dy$_{2}$(HL$^{1}$)(L$^{1}$)] (5), and [Ln$_{2}$(L$_{2}$)$_{2}$] (Ln = Tb$^{III}$ (7), Dy$^{III}$ (8)) supported by the hybrid Schiff-base/calix[4]arene ligands H$_{4}$L$^{1}$ (25-[2-((2-methylphenol)imino)ethoxy]-26,27,28-trihydroxy-calix[4]arene) and H$_{3}$L$^{2}$ (25-[2-((2-methylpyridine)imino)ethoxy]-26,27,28-trihydroxy-calix[4]arene) are reported. Spectroscopic data (for 5) and X-ray crystallographic analysis (for 7·4MeCN, 8·4MeCN) reveal the presence of dimeric structures, featuring doubly-bridged NO$_{4}$Ln(μ-O)$_{2}$LnO$_{4}$N (5) or N$_{2}$O$_{3}$Ln(μ-O)$_{2}$LnO$_{3}$N$_{2}$ cores (7, 8) with seven-coordinated Ln$^{3+}$ ions. The magnetic properties of polycrystalline samples of 5, 7 and 8 were studied by variable temperature dc and ac magnetic susceptibility measurements. The χ′′(T) vs. T plots show no maxima in zero field, but the maxima can be detected under a 3 kOe dc field. The relaxation times τ obey the Arrhenius law above 5 K. Anisotropy barriers of ∼18 cm$^{-1}$ (26 K) for 5 and ∼23 cm$^{-1}$ (33 K) for 8 were determined

Role of Oxygen Electrons in the Metal-Insulator Transition in the Magnetoresistive Oxide La2−2x_{2-2x}Sr1+2x_{1+2x}Mn2_2O7_7 Probed by Compton Scattering

We have studied the [100]-[110] anisotropy of the Compton profile in the bilayer manganite. Quantitative agreement is found between theory and experiment with respect to the anisotropy in the two metallic phases (i.e. the low temperature ferromagnetic and the colossal magnetoresistant phase under a magnetic field of 7 T). Robust signatures of the metal-insulator transition are identified in the momentum density for the paramagnetic phase above the Curie temperature. We interpret our results as providing direct evidence for the transition from the metallic-like to the admixed ionic-covalent bonding accompanying the magnetic transition. The number of electrons involved in this phase transition is estimated from the area enclosed by the Compton profile anisotropy differences. Our study demonstrates the sensitivity of the Compton scattering technique for identifying the number and type of electrons involved in the metal-insulator transition.Comment: 4 pages, 4 figures, accepted for publication in Physical Review Letter

Simian immunodeficiency virus infection in wild-caught chimpanzees from Cameroon

Simian immunodeficiency viruses (SIVcpz) infecting chimpanzees (Pan troglodytes) in west central Africa are the closest relatives to all major variants of human immunodeficiency virus type 1 ([HIV-1]; groups M, N and O), and have thus been implicated as the source of the human infections; however, information concerning the prevalence, geographic distribution, and subspecies association of SIVcpz still remains limited. In this study, we tested 71 wild-caught chimpanzees from Cameroon for evidence of SIVcpz infection. Thirty-nine of these were of the central subspecies (Pan troglodytes troglodytes), and 32 were of the Nigerian subspecies (Pan troglodytes vellerosus), as determined by mitochondrial DNA analysis. Serological analysis determined that one P. t. troglodytes ape (CAM13) harbored serum antibodies that cross-reacted strongly with HIV-1 antigens; all other apes were seronegative. To characterize the newly identified virus, 14 partially overlapping viral fragments were amplified from fecal virion RNA and concatenated to yield a complete SIVcpz genome (9,284 bp). Phylogenetic analyses revealed that SIVcpzCAM13 fell well within the radiation of the SIVcpzPtt group of viruses, as part of a clade including all other SIVcpzPtt strains as well as HIV-1 groups M and N. However, SIVcpzCAM13 clustered most closely with SIVcpzGAB1 from Gabon rather than with SIVcpzCAM3 and SIVcpzCAM5 from Cameroon, indicating the existence of divergent SIVcpzPtt lineages within the same geographic region. These data, together with evidence of recombination among ancestral SIVcpzPtt lineages, indicate long-standing endemic infection of central chimpanzees and reaffirm a west central African origin of HIV-1. Whether P. t. vellerosus apes are naturally infected with SIVcpz requires further study

Electrotransport and magnetic properies of Cr-GaSb spintronic materials synthesized under high pressure

Electrotarnsport and magnetic properties of new phases in the system Cr-GaSb were studied. The samples were prepared by high-pressure (P=6-8 GPa) high-temperature treatment and identified by x-ray diffraction and scanning electron microscopy (SEM). One of the CrGa$_2$Sb$_2$ phases with an orthorhombic structure $Iba2$ has a combination of ferromagnetic and semiconductor properties and is potentially promising for spintronic applications. Another high-temperature phase is paramagnetic and identified as tetragonal $I4/mcm$

A genome browser database for rice (Oryza sativa) and Chinese cabbage (Brassica rapa)

We have constructed an integrated genome browser database for sequence analysis of rice (Oryza sativa) and Chinese cabbage (Brassica rapa) genomes. The genome browser for Arabidopsis (Arabidopsis thaliana) was included to provide the comparative analysis with Chinese cabbage. Thegenome browser of rice provides a variety of alternate views of the data in 12 chromosomes. Constructed from a supercontig using 3,360 BACs, it shows information about individual genes with functional annotation in the whole chromosome. In addition, the rice genome browser provides specificanalysis of the genome by Gene Ontology (GO), single nucleotide polymorphisms (SNPs), Align, Text, Mart, BLAST and Export data views. In the comparative genome analysis between the Arabidopsis and Chinese cabbage genomes, users can obtain information using comparative genomics methods and identify missing regions within a single genome