From owner-chemistry@ccl.net Wed Nov 21 05:57:01 2012 From: "Martin Bohl martin[-]moldiscovery.com" To: CCL Subject: CCL: FLAP software released Message-Id: <-47891-121121053829-22808-nwXavcn0Io9hV0hHZmHa2w() server.ccl.net> X-Original-From: "Martin Bohl" Date: Wed, 21 Nov 2012 05:37:54 -0500 Sent to CCL by: "Martin Bohl" [martin(~)moldiscovery.com] Dear Colleagues, We would like to draw your attention to the release of FLAP 1.0 for virtual screening, pharmacophore modelling, and 3D-QSAR. FLAP is based on GRID Molecular Interaction Fields, in combination with pharmacophoric quadruplet fingerprints, and enables candidate similarity to be calculated to a template in both ligand-based and structure-based approaches. The fingerprints can be used directly to compare structure, or to perform ligand-based alignment and structure-based pose prediction. These alignments are scored according to GRID MIF similarity, allowing candidates to be ranked according to how well they match the template. A wide range of GRID MIF similarities can be calculated, including a global similarity score. Additionally, target specific scores can be parameterised using known active/inactive data to train the method. For virtual screening, FLAP has been validated against a number of prospective targets to find adenosine receptor antagonists, folate cycle inhibitors, NorA inhibitors, and influenza viruses. Pharmacophore elucidation can be performed from a set of active molecules, using the FLAPpharm approach that is based on FLAP ligand-based alignments. The approach has been validated on the PharmBench dataset; starting from known X-ray conformations the method was able to generate successful models in 94% of cases, and starting from 2D unbiased input gave 67% success according to an objective measure (rising to 83% including subjectively successful models). 3D-QSAR can be performed using the FLAP alignments, or alternatively a fuzzy maximal common subgraph based alignment, in addition to the GRID MIFs and statistical approaches such as PCA/PLS. Key features include: - Fast ligand-based and structure-based virtual screening using FLAP fingerprints - Improved virtual screening accuracy using FLAP alignment and GRID MIF scoring - Optional user-specified pharmacophoric feature constraints - Ligand-based alignment and structure-based pose prediction using GRID MIFs - Pharmacophore elucidation and screening - Automatic pocket detection for structure-based design - Linear Discriminant Analysis enables the training of target focused scoring functions - Enrichment plot analysis enables screening approach validation prior to prospective screening - Fuzzy maximal common substructure alignment - 3D-QSAR analysis - MoKa integration for automatic protonation and tautomer enumeration and selection (requires FLAP-Suite edition) FLAP is available for both Windows and Linux operating systems. More information about FLAP can be found here: http://www.moldiscovery.com/soft_flap.php Kind regards, Martin Dr. Martin Bohl Commercial Director Molecular Discovery Ltd Email: martin[at]moldiscovery[dot]com Molecular Discovery provides robust, high-quality and innovative computational methods addressing pharmaceutical needs in the field of drug discovery, including methods for virtual screening, lead optimisation, ADME modelling and metabolism research. Molecular Discovery software products offer calculation of accurate Molecular Interaction Fields for structure-based design (GRID), ligand-based and structure-based virtual screening (FLAP), pharmacophore elucidation (FLAP), metabolism prediction (MetaSite), metabolite identification (Mass-MetaSite), scaffold hopping (SHOP), pKa prediction (MoKa), 3D-QSAR modeling (FLAP, Pentacle) to improve efficiency in modern drug discovery. More information can be found on the main page: http://www.moldiscovery.com/ From owner-chemistry@ccl.net Wed Nov 21 23:13:00 2012 From: "Eric Scerri scerri##chem.ucla.edu" To: CCL Subject: CCL: Article on Structural realism in Chemistry in latest New Scientist Message-Id: <-47892-121121185229-3798-20ZFsZ8JWxBspU+TVmxpGA a server.ccl.net> X-Original-From: Eric Scerri Content-Type: multipart/alternative; boundary="Apple-Mail=_E7DBC2B1-64F8-443E-A9B3-93A0D7423DF5" Date: Wed, 21 Nov 2012 15:52:22 -0800 Mime-Version: 1.0 (Mac OS X Mail 6.2 \(1499\)) Sent to CCL by: Eric Scerri [scerri[*]chem.ucla.edu] --Apple-Mail=_E7DBC2B1-64F8-443E-A9B3-93A0D7423DF5 Content-Transfer-Encoding: quoted-printable Content-Type: text/plain; charset=us-ascii please see, = http://www.newscientist.com/article/mg21628920.200-are-you-really-a-realis= t.html full article available on request. =20 ericscerri.com On Twitter: =20 https://twitter.com/#!/ericscerri --Apple-Mail=_E7DBC2B1-64F8-443E-A9B3-93A0D7423DF5 Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset=us-ascii http://www.newscientist.com/article/mg21628920.200-are-you= -really-a-realist.html

full article = available on request.