QSAR and Library Design in Discovery Studio
QSAR and Library Design in Discovery Studio
QSAR and Library Design in Discovery Studio
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Advanced tools forcreat<strong>in</strong>g optimalchemical libraries<strong>Discovery</strong> <strong>Studio</strong><strong>QSAR</strong> <strong>and</strong> <strong>Library</strong> <strong>Design</strong> <strong>in</strong> <strong>Discovery</strong> <strong>Studio</strong>Pareto Optimizationfor simultaneousmultivariableenhancementAn extensive set of<strong>QSAR</strong> descriptors <strong>and</strong>seamless <strong>in</strong>tegrationof additional data<strong>in</strong>to <strong>QSAR</strong> modelsThe Power of <strong>QSAR</strong> <strong>and</strong> <strong>Library</strong> <strong>Design</strong>The ultimate objective of many computational model<strong>in</strong>g studies is to identify compoundsthat could potentially become new drugs. With appropriate molecular descriptors, thelarge quantity of relatively easily available data <strong>in</strong>herent <strong>in</strong> chemical libraries can bem<strong>in</strong>ed, analyzed <strong>and</strong> used to select compounds that can become drug leads.DS <strong>QSAR</strong> provides easy access to the hundreds of molecular descriptors, proven <strong>in</strong> biologicalsystems to correlate with activity. The streaml<strong>in</strong>ed <strong>Discovery</strong> <strong>Studio</strong>® (DS) <strong>in</strong>terface presentsthese descriptors <strong>and</strong> advanced model<strong>in</strong>g <strong>and</strong> visualization methods <strong>in</strong> an easy-to-useenvironment. DS <strong>Library</strong> <strong>Design</strong> applies these capabilities together with similarity <strong>and</strong> diversitymethods specifically tailored for chemical library design to guide optimal library design.Accelrys ScienceExtensive Set of Proven Descriptors to EffectivelyCapture Critical Properties <strong>in</strong> DS <strong>QSAR</strong>• Describe billions of structural features present<strong>in</strong> molecules us<strong>in</strong>g Extended ConnectivityF<strong>in</strong>gerpr<strong>in</strong>t (ECFP) descriptors.• Access traditional descriptors for basicchemical features, physical properties, ADMEcharacteristics, <strong>and</strong> experimental data.• Optionally add VAMP <strong>and</strong> DMol 3 for efficientimplementations of semi-empirical quantummechanical methods to rapidly calculatehighly accurate electronic properties forthous<strong>and</strong>s of c<strong>and</strong>idate compounds.Advanced Model<strong>in</strong>g Tools for Easy Analysis ofComplex Data <strong>in</strong> DS <strong>QSAR</strong>• Easily apply model<strong>in</strong>g techniques such asBayesian models, multiple l<strong>in</strong>ear regression,Partial Least Squares (PLS), Genetic FunctionalAnalysis <strong>and</strong> more.• Extend the basic functionality of the packageby add<strong>in</strong>g an advanced neural networkcomponent <strong>and</strong> quantum mechanical baseddescriptors.Powerful, Customizable, <strong>and</strong> Easily AccessibleSAR Tools <strong>in</strong> DS <strong>QSAR</strong>• Integrated <strong>Discovery</strong> <strong>Studio</strong> environmentprovides easy access to <strong>QSAR</strong> tools along sidelibrary design <strong>and</strong> other tools.• Us<strong>in</strong>g the Pipel<strong>in</strong>e Pilot Platform, <strong>QSAR</strong>models can easily be deployed to <strong>and</strong> sharedamong large groups of chemists.• Advanced 3D graph<strong>in</strong>g <strong>and</strong> molecular dataviews guide users <strong>in</strong> draw<strong>in</strong>g conclusionsfrom complex data.Easily <strong>Design</strong> Targeted Chemical Libraries withDS <strong>Library</strong> <strong>Design</strong>• Maximize multiple properties simultaneouslyus<strong>in</strong>g Pareto Optimization methods.• Prioritize chemical libraries us<strong>in</strong>g readilyaccessible metrics for diversity, similarity, <strong>and</strong>hundreds of physical <strong>and</strong> chemical properties.• Interactively customize chemical librariesto optimize the value of each member of aselected set of compounds.
<strong>Discovery</strong> <strong>Studio</strong>Figure 1 An <strong>in</strong>teractive MultipleL<strong>in</strong>ear Regression <strong>QSAR</strong> modelshow<strong>in</strong>g correlation betweenactual <strong>and</strong> predicted activities.Selection between the plot <strong>and</strong>table are synchronized.The Gold St<strong>and</strong>ard <strong>in</strong> TechnologyComprehensive – The <strong>QSAR</strong> <strong>and</strong> library design tools<strong>in</strong> <strong>Discovery</strong> <strong>Studio</strong> <strong>in</strong>clude hundreds of usefuldescriptors, multiple well validated model build<strong>in</strong>gtechniques <strong>and</strong> tools specially tailored for customlibrary selection <strong>and</strong> design. These packages caneasily be augmented with powerful add-ons forrapidly generat<strong>in</strong>g quantum mechanical baseddescriptors <strong>and</strong> advanced model<strong>in</strong>g techniques.Proven history – The core technology has undergoneover a dozen years of cont<strong>in</strong>uous <strong>in</strong>novation<strong>and</strong> customer driven improvement, <strong>and</strong> hasdemonstrated dependable performance <strong>in</strong> thepharmaceutical <strong>in</strong>dustry with dozens of publications.Cutt<strong>in</strong>g edge – Accelrys is <strong>in</strong>corporat<strong>in</strong>g newscientific tools to meet current pharmaceuticalneeds <strong>and</strong> we are cont<strong>in</strong>uously work<strong>in</strong>g with ourcustomers to plan for future <strong>in</strong>novation.Easy to use <strong>in</strong>terface – DS 2.0 provides apowerful <strong>and</strong> <strong>in</strong>tuitive user <strong>in</strong>terface. DS 2.0can be deployed either <strong>in</strong> a complete st<strong>and</strong>alonesolution for <strong>in</strong>dividual modelers or as part of anenterprise-level client server <strong>in</strong>stallation for easierprotocol shar<strong>in</strong>g <strong>and</strong> adm<strong>in</strong>istration <strong>in</strong> largermodel<strong>in</strong>g groups.Integrated solution – The DS 2.0 environment, basedon the Pipel<strong>in</strong>e Pilot open operat<strong>in</strong>g platform,<strong>in</strong>tegrates prote<strong>in</strong> model<strong>in</strong>g, pharmacophoreanalysis, <strong>and</strong> virtual screen<strong>in</strong>g as well as thirdpartyapplications for an <strong>in</strong>f<strong>in</strong>itely extensiblevirtual discovery platform. Well-tested applications<strong>in</strong>clud<strong>in</strong>g CHARMm, MODELER, Catalyst, <strong>and</strong> othersare accessible <strong>in</strong> the graphical DS environment, thePipel<strong>in</strong>e Pilot script<strong>in</strong>g <strong>and</strong> protocol developmentenvironment <strong>and</strong> from comm<strong>and</strong>-l<strong>in</strong>e prompts.Parallel comput<strong>in</strong>g – The DS 2.0 platform isoptimized to take advantage of grid <strong>and</strong> clustercomput<strong>in</strong>g as well as multi-core processors torapidly process large tasks.Accelrys is Your Partner <strong>in</strong> ResearchUser community – Accelrys scientific forums<strong>and</strong> presentations at scientific meet<strong>in</strong>gs worldwideprovide opportunities for Accelrys users toexchange ideas <strong>and</strong> share new research.Scientific consult<strong>in</strong>g – Accelrys has dozensof experienced Ph.D.s with expertise <strong>in</strong>implement<strong>in</strong>g scientific solutions for drugdesign that are available for short or long-termengagements to create tailored solutions orperform model<strong>in</strong>g experiments.
<strong>Discovery</strong> <strong>Studio</strong>Figure 2 An <strong>in</strong>teractive 3D plot ofthe first three pr<strong>in</strong>cipal componentsfrom a Pr<strong>in</strong>cipal ComponentAnalysis us<strong>in</strong>g several moleculardescriptors as <strong>in</strong>put. The plot canoptionally be colored by a specifiedproperty.Customer support – Accelrys customers report a98% satisfaction rate with our support team.Committed to <strong>in</strong>novation – With over 100 Ph.D.s <strong>in</strong>the field work<strong>in</strong>g daily with researchers <strong>in</strong> <strong>in</strong>dustry<strong>and</strong> academia, Accelrys is committed to deliver<strong>in</strong>gcutt<strong>in</strong>g-edge technology to our customersWorld lead<strong>in</strong>g scientific advisors – Through our<strong>in</strong>-licens<strong>in</strong>g agreements, partnerships, <strong>and</strong> scientificadvisors many of the world’s foremost experts <strong>in</strong>computational drug design are <strong>in</strong>volved <strong>in</strong> sett<strong>in</strong>gour direction.Biological Validation <strong>and</strong>Comparison2007 – Genetic Functional Analysis module used tostudy fluoroqu<strong>in</strong>olone antibacterials. The resultssuggest specific chemical modifications <strong>and</strong>physical properties for future drug design efforts. 12006 – Effect of 2-am<strong>in</strong>othiazole derivatives onNeuro-cell apoptosis studied us<strong>in</strong>g a <strong>QSAR</strong> modelthat has a 97% correlation to EC 5022003 – A descriptor-based <strong>QSAR</strong> model for hOCT1predicts IC 50values with 95% correlation toobserved data. 3References:1.2.3.Cheg, D. et al., “Relationship of quantitative structure <strong>and</strong> pharmacok<strong>in</strong>etics <strong>in</strong> fluoroqu<strong>in</strong>olone antibacterials”,World J Gastroenterol, 2007, 13(17), 2496-503Jiang FC., et al., “The design <strong>and</strong> synthesis of 2-am<strong>in</strong>othiazole derivatives <strong>and</strong> their <strong>in</strong>hibitory activity on apoptosis”,Yao Xue Xue Bao, 2006, 41(8), 727-34Bednarczyk D., et al., “Influence of molecular structure on substrate b<strong>in</strong>d<strong>in</strong>g to the human organic cation transporter, hOCT”,Mol. Pharmacol, 2003, 63(3), 489-980907