There is a long-standing philosophical (and largely semantic) debate as to whether viruses should ever be considered to be alive [194]. A more practical consideration is whether or not viruses detected in a microbial community are infective, that is, still capable of infecting host cells. While the use of PMA to distinguish between infective and non-infective bacteriophage can be effective, this technique does not work on all viruses. For example, results from murine noroviruses showed that, while PMA could be used to distinguish between viable and non-viable virions, quantitative PCR following PMA treatment did not agree with culture-based results [66]. Recently, partial viral genomes (human cyclovirus 7078A and Propionibacterium phage P14.4) were reconstructed from clean room samples post-PMA treatment, potentially indicating the recovery of virions with intact capsids, and/or of viral genomes incorporated in viable bacterial cells [39]. The combined detection of both nucleic acids and capsid proteins (via proteomics or metaproteomics) may be more indicative of an infectious particle than nucleic acid detection alone [171], though viral proteomics seems to be better suited to identifying structural components of virions, rather than inferring viral infectivity [195, 196].
Many of our anticancer programs have a computational chemistry-directed focus, relying on molecular modeling based upon published coordinates, virtual screening, scoring, and validation of predicted hits through chemical synthesis. We use the Schrodinger suite of modeling software in these studies. For future work we may have a need to hire postdoctoral scientists with both computational and synthesis experience. Please contact me for further information.
Schrodinger Suite 2010.torrent
On occasion I have openings for outstanding postdoctoral fellows in my labs. As mentioned above, an especially good fit would be a postdoc with lab synthesis experience and with prior expertise in using the Schrodinger suite of molecular modeling software, to aid our virtual screening-based efforts. Our postdoctoral scientists collaborate with a team of biological co-investigators, applying knowledge and experience in modern organic, heterocyclic, and/or medicinal chemistry toward an ongoing drug discovery effort. Excellent communication skills, good synthetic organic chemistry laboratory skills, ability to work in the US, and familiarity with modern synthetic techniques and instrumentation are required in this role. Contact me for further details.
Despite what many people believe, Wine is used not only to run "simple" Windows applications, but even complex games. What's more, it has been proven that terrible games like Sim 3, Half Life 2, Command & Conquer 3, Star Wars: Jedi Knight, or important suites like Microsoft Office work perfectly.
GPCRs contain a wide variety of allosteric sites and their targeting with small molecules offers unique therapeutic potential [3,4,5]. As it has been discussed recently [6] allosteric sites are widely distributed intrahelically in the TM bundle, at extrahelical positions within the membrane binding region and at the intracellular signalling protein interface. These sites may or may not be preformed before ligand binding and they are generally sensitive to protein conformational changes and to the presence of and the interactions with water molecules. We selected the metabotropic glutamate receptor 5 (mGlu5 receptor) for a detailed investigation because its allosteric site is structurally well characterized owing to the receptor complexes co-crystallized with a variety of allosteric ligands [7,8,9,10]. Moreover, a wide range of allosteric ligands with biochemical data have been reported. Therefore, the mGlu5 receptor is well suited to investigate how virtual screening can find allosteric ligands and what are the special considerations needed for maximizing its value in allosteric ligand discovery. Metabotropic glutamate receptors belong to the family C of GPCRs, and can influence neurotransmitter release or modulate ion channel activity [11]. Their endogen ligand is l-glutamic acid, a major excitatory neurotransmitter in the central nervous system (CNS) of mammals. Modulation of glutamate transmission has a potential in the treatment of several psychiatric and neurological disorders. Glutamate binds to the extracellular Venus flytrap domain that is linked to the seven transmembrane domain through a cysteine-rich domain. Non-competitive antagonists which bind in the allosteric site are called negative allosteric modulators (NAMs), and could be useful in the treatment of numerous diseases [12]. 2ff7e9595c
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