Virtual Libraries and Virtual Screening in Drug Discovery Processes using KNIME
|
|
- Trevor Hunt
- 5 years ago
- Views:
Transcription
1 Virtual Libraries and Virtual Screening in Drug Discovery Processes using KNIME Iván Solt Solutions for Cheminformatics
2 Drug Discovery Strategies for known targets High-Throughput Screening (HTS) Cells or recombinant protein Fluorescent or luminescent readout Automated, miniaturized Thousands of samples / day Number of primer actives: ~1% Virtual Screening (VS) Ligand or structure based Virtual or real libraries Similarity search, 2D or 3D Can lead to thousands of possible actives: further processing needed Measurement: Enrichment ratio, ROC curves for known actives
3 Virtual Library Design Workflow DB DB Databases Reactions Molecules Queries Fragmentation R-group decomposition Fragmentation Reagent clipping Compound selection Similarity searches Substructure searches Enumeration Fuse fragments R-group composition Reaction enumeration Library analysis Clustering 2D similarity screen 3D Shape similarity screen
4 Find or Virtually Create Candidates Virtual screening of existing compounds Pros: Fast Hits are readily available for in vitro experiments Cons: Limitation on available compounds De novo design Pros: No limitation on virtual compound space Structural novelty Cons: Are hits synthetically available?
5 Find or Virtually Create Candidates Virtual screening of existing compounds Pros: Fast Hits are readily available for in vitro experiments Cons: Limitation on available compounds De novo design Pros: No limitation on virtual compound space Structural novelty Cons: Are hits synthetically available?
6 Virtual Screening Workflow DB DB Molecules in-house or commercially available 1. Reactions virtual synthetic path Synthetically Accessible Compounds 2. Filtering in vivo experiment? 5. Clustering 4. 3D alignment 3. Similarity Search
7 Step 1: Reaction Enumeration Reaction schema for accessible syntheses Combinatorial or sequential enumeration Reaction rules: phrase + apply public and in-house chemical knowledge Selectivity with tolerance Reactivity Exclusion rules EXCLUDE: match(reactant(1), "[Cl,Br,I]C(=[O,S])C=C") or match(reactant(0), "[H][O,S]C=[O,S]") or match(reactant(0), "[P][H]") or (max(pka(reactant(0), filter(reactant(0), "match('[o,s;h1]')"), "acidic")) > 14.5) or (max(pka(reactant(0), filter(reactant(0), "match('[#7:1][h]', 1)"), "basic")) > 0)
8 Step 1: Reaction Enumeration
9 Step 1: Reaction Enumeration Reaction rules ON Fewer results than theoretical Unfeasible starting materials eliminated Feasible products only Custom rules can be added to increase selectivity Reaction rules OFF More results Best for debugging purposes Prodcts may be incorrect due to neglecting chemical rules
10 Step 2: Filtering Lead likeness, drug likeness Chemical Terms Could it fit to the active centre? Basic analysis: size, mass... Could it get to the active centre? ADME properties: solubility, pka, polar surface, partition coefficients... Structural filtering e.g. reactive groups Toxicity, environmental concerns, etc... Calculator plugins Elemental Analysis Elemental Analysis IUPAC Name Structure to Name Protonation pk a Microspecies Isoelectric Point Partitioning logp logd Charge Charge Polarizability Orbital Electronegetivity Isomers Tautomerization Stereoisomer Conformation Conformer Flexible 3D Alignment Molecular Dynamics Geometry Topology Analysis Geometry Polar Surface Area (2D) Molecular Surface Area (3D) Markush Markush Enumeration Other Hydrogen Bond Donor- Acceptor Huckel Analysis Refractivity Structural Framework Resonance
11 Step 3: Similarity search Screen 2D + Descriptor package Screen against known bioactives Chemical Fingerprints Topology Pharmacophore Fingerprints: Custom atomic properties + their topological relationship H-bond donors / acceptors Cationic / anionic groups Hydrophobic groups Aromatic groups etc. ECFP/FCFP Similarity searches Tanimoto, Eucledian, Tversky metrics Metrics optimization regular Tanimoto optimized Tanimoto
12 Step 4: Screen 3D Align the candidates to the known active in 3D Treat the candidate flexible! Consider pharmacophore atom types (align cationic to cationic, etc.)! Problem: complicated conformational space
13 Step 4: Screen 3D Simple sampling of the conformational space: Minimum and maximum distance between atom pairs in the full torsion space Select atoms Colors (e.g. pharmacophore types ) Topological features (e.g.:longest chain start/end/center) Ring centers (aromatic, aliphatic) Calculate Min/max internal distance ranges Distance histograms for selected atoms Only once for each molecule
14 Step 4: Screen 3D Hybrid alignment: Separate translation&rotation from torsions Robust and goes fast Needs good guess on atomatom mapping: Same colors Distance ranges must be allowed for all mapped pairs Triangle inequality must be fulfilled for any atom triplet
15 % of the actives retrieved Screen 3D: Test on DUD 30 Average of 1% Enrichments Giganti et al. J. Chem. Inf. Model. 2010, 50, 992
16 % of the actives retrieved Screen 3D: Test on DUD 100 Average of 10% enrichments Giganti et al. J. Chem. Inf. Model. 2010, 50, 992
17 Screen 3D: Test on DUD Average time per compound (without precalculations) ChemAxon Screen3D 0.07 ROCS 0.5 FRED 1.0 ICMsim 2.4 Surflex-sim 6.7 FlexS 6.9 Surflex-dock 14.6 FLEXX 15.6 ICM 17.7 Speed Intel Q GHz Intel Xeon 2.4 GHz Giganti et al. J. Chem. Inf. Model. 2010, 50, 992
18 Step 5: Clustering, library analysis JKlustor Wide range of methods Unsupervised, agglomerative clustering Hierarchical and non-hierarchical methods Similarity based and structure based techniques Flexible search options Tanimoto and Euclidean metrics, weighting Maximum common substructure identification chemical property matching including atom type, bond type, hybridization, charge
19 JChem Extensions in KNIME Worklflow management in KNIME JChem extension nodes developed by InfoCom, Japan Constantly developing palette of available JChem tools
20 JChem Extensions in KNIME IO molecule and reaction import, export, drawing Visualization Manipulators Calculator plugins Reactor Similarity and structure-based search Fingerprint calculation Fragmentation Clustering R-group composition, decompozition Standardization... Database management Molecular format conversion Web search services
21 Step 1: Reaction Enumeration
22 Step 2: Filtering
23 Step 2: Filtering
24 Step 3: Similarity search
25 JChem Extensions in KNIME DB DB 1. Reactions virtual synthetic path Synthetically Accessible Compounds 2. Filtering in vivo experiment? 4. 3D alignment 3. Similarity Search 1. Import reactants 2. Enumerate reaction Carry out topology analysis 3. Calculate properties Filter 4. Screen for similarity against known active 5. Export results
26 Conclusions Virtual libraries and virtual screening are essential tools in modern Drug Discovery No special hardware, short experiment cycles, variety of approaches Database of synthetically accessible compounds can be designed with reaction libraries and custom in-house synthetic knowledge Powerful 3D alignment techniques allow highthroughput conformational screening with great efficiency Straightforward integration into KNIME
27 Contributors Tímea Polgár Attila Tajti
28
Pipeline Pilot Integration
Scientific & technical Presentation Pipeline Pilot Integration Szilárd Dóránt July 2009 The Component Collection: Quick facts Provides access to ChemAxon tools from Pipeline Pilot Free of charge Open source
More informationMarvin. Sketching, viewing and predicting properties with Marvin - features, tips and tricks. Gyorgy Pirok. Solutions for Cheminformatics
Marvin Sketching, viewing and predicting properties with Marvin - features, tips and tricks Gyorgy Pirok Solutions for Cheminformatics The Marvin family The Marvin toolkit provides web-enabled components
More informationPipeline Pilot Integration
Pipeline Pilot Integration Szilard Dorant Solutions for Cheminformatics The Component Collection: Quick facts Provides access to ChemAxon tools from Pipeline Pilot Developed and Supported by ChemAxon Free
More informationData Mining in the Chemical Industry. Overview of presentation
Data Mining in the Chemical Industry Glenn J. Myatt, Ph.D. Partner, Myatt & Johnson, Inc. glenn.myatt@gmail.com verview of presentation verview of the chemical industry Example of the pharmaceutical industry
More informationBiologically Relevant Molecular Comparisons. Mark Mackey
Biologically Relevant Molecular Comparisons Mark Mackey Agenda > Cresset Technology > Cresset Products > FieldStere > FieldScreen > FieldAlign > FieldTemplater > Cresset and Knime About Cresset > Specialist
More informationMethods for tautomer enumeration, -searching and -duplicate filtering
Methods for tautomer enumeration, -searching and -duplicate filtering József Szegezdi, Zsolt Mohácsi, Tamás Csizmazia, Szilárd Dóránt, Ákos Papp, György Pirok, Szabolcs Csepregi, Ferenc Csizmadia Solutions
More informationSimilarity Search. Uwe Koch
Similarity Search Uwe Koch Similarity Search The similar property principle: strurally similar molecules tend to have similar properties. However, structure property discontinuities occur frequently. Relevance
More informationIntroduction to Chemoinformatics and Drug Discovery
Introduction to Chemoinformatics and Drug Discovery Irene Kouskoumvekaki Associate Professor February 15 th, 2013 The Chemical Space There are atoms and space. Everything else is opinion. Democritus (ca.
More informationComputational Chemistry in Drug Design. Xavier Fradera Barcelona, 17/4/2007
Computational Chemistry in Drug Design Xavier Fradera Barcelona, 17/4/2007 verview Introduction and background Drug Design Cycle Computational methods Chemoinformatics Ligand Based Methods Structure Based
More informationThe Schrödinger KNIME extensions
The Schrödinger KNIME extensions Computational Chemistry and Cheminformatics in a workflow environment Jean-Christophe Mozziconacci Volker Eyrich Topics What are the Schrödinger extensions? Workflow application
More informationest Drive K20 GPUs! Experience The Acceleration Run Computational Chemistry Codes on Tesla K20 GPU today
est Drive K20 GPUs! Experience The Acceleration Run Computational Chemistry Codes on Tesla K20 GPU today Sign up for FREE GPU Test Drive on remotely hosted clusters www.nvidia.com/gputestd rive Shape Searching
More informationIntroduction. OntoChem
Introduction ntochem Providing drug discovery knowledge & small molecules... Supporting the task of medicinal chemistry Allows selecting best possible small molecule starting point From target to leads
More informationThe PhilOEsophy. There are only two fundamental molecular descriptors
The PhilOEsophy There are only two fundamental molecular descriptors Where can we use shape? Virtual screening More effective than 2D Lead-hopping Shape analogues are not graph analogues Molecular alignment
More informationUsing AutoDock for Virtual Screening
Using AutoDock for Virtual Screening CUHK Croucher ASI Workshop 2011 Stefano Forli, PhD Prof. Arthur J. Olson, Ph.D Molecular Graphics Lab Screening and Virtual Screening The ultimate tool for identifying
More informationChemAxon. Content. By György Pirok. D Standardization D Virtual Reactions. D Fragmentation. ChemAxon European UGM Visegrad 2008
Transformers f off ChemAxon By György Pirok Content Standardization Virtual Reactions Metabolism M b li P Prediction di i Fragmentation 2 1 Standardization http://www.chemaxon.com/jchem/doc/user/standardizer.html
More informationNavigation in Chemical Space Towards Biological Activity. Peter Ertl Novartis Institutes for BioMedical Research Basel, Switzerland
Navigation in Chemical Space Towards Biological Activity Peter Ertl Novartis Institutes for BioMedical Research Basel, Switzerland Data Explosion in Chemistry CAS 65 million molecules CCDC 600 000 structures
More informationIn Silico Investigation of Off-Target Effects
PHARMA & LIFE SCIENCES WHITEPAPER In Silico Investigation of Off-Target Effects STREAMLINING IN SILICO PROFILING In silico techniques require exhaustive data and sophisticated, well-structured informatics
More informationPractical QSAR and Library Design: Advanced tools for research teams
DS QSAR and Library Design Webinar Practical QSAR and Library Design: Advanced tools for research teams Reservationless-Plus Dial-In Number (US): (866) 519-8942 Reservationless-Plus International Dial-In
More informationUsing Phase for Pharmacophore Modelling. 5th European Life Science Bootcamp March, 2017
Using Phase for Pharmacophore Modelling 5th European Life Science Bootcamp March, 2017 Phase: Our Pharmacohore generation tool Significant improvements to Phase methods in 2016 New highly interactive interface
More informationDrug Informatics for Chemical Genomics...
Drug Informatics for Chemical Genomics... An Overview First Annual ChemGen IGERT Retreat Sept 2005 Drug Informatics for Chemical Genomics... p. Topics ChemGen Informatics The ChemMine Project Library Comparison
More informationUsing Self-Organizing maps to accelerate similarity search
YOU LOGO Using Self-Organizing maps to accelerate similarity search Fanny Bonachera, Gilles Marcou, Natalia Kireeva, Alexandre Varnek, Dragos Horvath Laboratoire d Infochimie, UM 7177. 1, rue Blaise Pascal,
More informationAn Integrated Approach to in-silico
An Integrated Approach to in-silico Screening Joseph L. Durant Jr., Douglas. R. Henry, Maurizio Bronzetti, and David. A. Evans MDL Information Systems, Inc. 14600 Catalina St., San Leandro, CA 94577 Goals
More informationThe Schrödinger KNIME extensions
The Schrödinger KNIME extensions Computational Chemistry and Cheminformatics in a workflow environment Jean-Christophe Mozziconacci Volker Eyrich KNIME UGM, Berlin, February 2015 The Schrödinger Extensions
More informationICM-Chemist How-To Guide. Version 3.6-1g Last Updated 12/01/2009
ICM-Chemist How-To Guide Version 3.6-1g Last Updated 12/01/2009 ICM-Chemist HOW TO IMPORT, SKETCH AND EDIT CHEMICALS How to access the ICM Molecular Editor. 1. Click here 2. Start sketching How to sketch
More informationIn silico pharmacology for drug discovery
In silico pharmacology for drug discovery In silico drug design In silico methods can contribute to drug targets identification through application of bionformatics tools. Currently, the application of
More informationBioSolveIT. A Combinatorial Approach for Handling of Protonation and Tautomer Ambiguities in Docking Experiments
BioSolveIT Biology Problems Solved using Information Technology A Combinatorial Approach for andling of Protonation and Tautomer Ambiguities in Docking Experiments Ingo Dramburg BioSolve IT Gmb An der
More informationContents 1 Open-Source Tools, Techniques, and Data in Chemoinformatics
Contents 1 Open-Source Tools, Techniques, and Data in Chemoinformatics... 1 1.1 Chemoinformatics... 2 1.1.1 Open-Source Tools... 2 1.1.2 Introduction to Programming Languages... 3 1.2 Chemical Structure
More informationLigandScout. Automated Structure-Based Pharmacophore Model Generation. Gerhard Wolber* and Thierry Langer
LigandScout Automated Structure-Based Pharmacophore Model Generation Gerhard Wolber* and Thierry Langer * E-Mail: wolber@inteligand.com Pharmacophores from LigandScout Pharmacophores & the Protein Data
More informationDr. Sander B. Nabuurs. Computational Drug Discovery group Center for Molecular and Biomolecular Informatics Radboud University Medical Centre
Dr. Sander B. Nabuurs Computational Drug Discovery group Center for Molecular and Biomolecular Informatics Radboud University Medical Centre The road to new drugs. How to find new hits? High Throughput
More informationFast similarity searching making the virtual real. Stephen Pickett, GSK
Fast similarity searching making the virtual real Stephen Pickett, GSK Introduction Introduction to similarity searching Use cases Why is speed so crucial? Why MadFast? Some performance stats Implementation
More informationBioengineering & Bioinformatics Summer Institute, Dept. Computational Biology, University of Pittsburgh, PGH, PA
Pharmacophore Model Development for the Identification of Novel Acetylcholinesterase Inhibitors Edwin Kamau Dept Chem & Biochem Kennesa State Uni ersit Kennesa GA 30144 Dept. Chem. & Biochem. Kennesaw
More informationStructural biology and drug design: An overview
Structural biology and drug design: An overview livier Taboureau Assitant professor Chemoinformatics group-cbs-dtu otab@cbs.dtu.dk Drug discovery Drug and drug design A drug is a key molecule involved
More informationIntegrated Cheminformatics to Guide Drug Discovery
Integrated Cheminformatics to Guide Drug Discovery Matthew Segall, Ed Champness, Peter Hunt, Tamsin Mansley CINF Drug Discovery Cheminformatics Approaches August 23 rd 2017 Optibrium, StarDrop, Auto-Modeller,
More informationQSAR Modeling of ErbB1 Inhibitors Using Genetic Algorithm-Based Regression
APPLICATION NOTE QSAR Modeling of ErbB1 Inhibitors Using Genetic Algorithm-Based Regression GAINING EFFICIENCY IN QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIPS ErbB1 kinase is the cell-surface receptor
More informationReceptor Based Drug Design (1)
Induced Fit Model For more than 100 years, the behaviour of enzymes had been explained by the "lock-and-key" mechanism developed by pioneering German chemist Emil Fischer. Fischer thought that the chemicals
More informationUltra High Throughput Screening using THINK on the Internet
Ultra High Throughput Screening using THINK on the Internet Keith Davies Central Chemistry Laboratory, Oxford University Cathy Davies Treweren Consultants, UK Blue Sky Objectives Reduce Development Failures
More informationBioSolveIT. A Combinatorial Docking Approach for Dealing with Protonation and Tautomer Ambiguities
BioSolveIT Biology Problems Solved using Information Technology A Combinatorial Docking Approach for Dealing with Protonation and Tautomer Ambiguities Ingo Dramburg BioSolve IT Gmb An der Ziegelei 75 53757
More informationSCULPT 3.0. Using SCULPT to Gain Competitive Insights. Brings 3D Visualization to the Lab Bench SPECIAL REPORT. 4 Molecular Connection Fall 1999
SPECIAL REPORT SCULPT 3.0 Brings 3D Visualization to the Lab Bench ith the acquisition of Interactive Simulations, Inc., last April, MDL added to its arsenal of discovery informatics tools a powerful analysis
More informationLigand Scout Tutorials
Ligand Scout Tutorials Step : Creating a pharmacophore from a protein-ligand complex. Type ke6 in the upper right area of the screen and press the button Download *+. The protein will be downloaded and
More informationReaxys Medicinal Chemistry Fact Sheet
R&D SOLUTIONS FOR PHARMA & LIFE SCIENCES Reaxys Medicinal Chemistry Fact Sheet Essential data for lead identification and optimization Reaxys Medicinal Chemistry empowers early discovery in drug development
More informationKNIME-based scoring functions in Muse 3.0. KNIME User Group Meeting 2013 Fabian Bös
KIME-based scoring functions in Muse 3.0 KIME User Group Meeting 2013 Fabian Bös Certara Mission: End-to-End Model-Based Drug Development Certara was formed by acquiring and integrating Tripos, Pharsight,
More informationChemoinformatics and information management. Peter Willett, University of Sheffield, UK
Chemoinformatics and information management Peter Willett, University of Sheffield, UK verview What is chemoinformatics and why is it necessary Managing structural information Typical facilities in chemoinformatics
More informationChemogenomic: Approaches to Rational Drug Design. Jonas Skjødt Møller
Chemogenomic: Approaches to Rational Drug Design Jonas Skjødt Møller Chemogenomic Chemistry Biology Chemical biology Medical chemistry Chemical genetics Chemoinformatics Bioinformatics Chemoproteomics
More informationThe Conformation Search Problem
Jon Sutter Senior Manager Life Sciences R&D jms@accelrys.com Jiabo Li Senior Scientist Life Sciences R&D jli@accelrys.com CAESAR: Conformer Algorithm based on Energy Screening and Recursive Buildup The
More informationEnamine Golden Fragment Library
Enamine Golden Fragment Library 14 March 216 1794 compounds deliverable as entire set or as selected items. Fragment Based Drug Discovery (FBDD) [1,2] demonstrates remarkable results: more than 3 compounds
More informationFarewell, PipelinePilot Migrating the Exquiron cheminformatics platform to KNIME and the ChemAxon technology
Farewell, PipelinePilot Migrating the Exquiron cheminformatics platform to KNIME and the ChemAxon technology Serge P. Parel, PhD ChemAxon User Group Meeting, Budapest 21 st May, 2014 Outline Exquiron Who
More informationBuilding innovative drug discovery alliances. Just in KNIME: Successful Process Driven Drug Discovery
Building innovative drug discovery alliances Just in KIME: Successful Process Driven Drug Discovery Berlin KIME Spring Summit, Feb 2016 Research Informatics @ Evotec Evotec s worldwide operations 2 Pharmaceuticals
More informationReaxys Pipeline Pilot Components Installation and User Guide
1 1 Reaxys Pipeline Pilot components for Pipeline Pilot 9.5 Reaxys Pipeline Pilot Components Installation and User Guide Version 1.0 2 Introduction The Reaxys and Reaxys Medicinal Chemistry Application
More informationDECEMBER 2014 REAXYS R201 ADVANCED STRUCTURE SEARCHING
DECEMBER 2014 REAXYS R201 ADVANCED STRUCTURE SEARCHING 1 NOTES ON REAXYS R201 THIS PRESENTATION COMMENTS AND SUMMARY Outlines how to: a. Perform Substructure and Similarity searches b. Use the functions
More informationChemical library design
Chemical library design Pavel Polishchuk Institute of Molecular and Translational Medicine Palacky University pavlo.polishchuk@upol.cz Drug development workflow Vistoli G., et al., Drug Discovery Today,
More informationExpanding the scope of literature data with document to structure tools PatentInformatics applications at Aptuit
Expanding the scope of literature data with document to structure tools PatentInformatics applications at Aptuit Alfonso Pozzan Computational and Analytical Chemistry Drug Design and Discovery Department
More informationComputational chemical biology to address non-traditional drug targets. John Karanicolas
Computational chemical biology to address non-traditional drug targets John Karanicolas Our computational toolbox Structure-based approaches Ligand-based approaches Detailed MD simulations 2D fingerprints
More informationKd = koff/kon = [R][L]/[RL]
Taller de docking y cribado virtual: Uso de herramientas computacionales en el diseño de fármacos Docking program GLIDE El programa de docking GLIDE Sonsoles Martín-Santamaría Shrödinger is a scientific
More informationCommand-line tools of ChemAxon: tips and tricks
Command-line tools of ChemAxon: tips and tricks György Pirok Solutions for Cheminformatics Command-line interface A command-line interface (CLI) is a mechanism for interacting with a computer operating
More informationAdvanced Medicinal Chemistry SLIDES B
Advanced Medicinal Chemistry Filippo Minutolo CFU 3 (21 hours) SLIDES B Drug likeness - ADME two contradictory physico-chemical parameters to balance: 1) aqueous solubility 2) lipid membrane permeability
More informationDrug Design 2. Oliver Kohlbacher. Winter 2009/ QSAR Part 4: Selected Chapters
Drug Design 2 Oliver Kohlbacher Winter 2009/2010 11. QSAR Part 4: Selected Chapters Abt. Simulation biologischer Systeme WSI/ZBIT, Eberhard-Karls-Universität Tübingen Overview GRIND GRid-INDependent Descriptors
More informationTautomerism in chemical information management systems
Tautomerism in chemical information management systems Dr. Wendy A. Warr http://www.warr.com Tautomerism in chemical information management systems Author: Wendy A. Warr DOI: 10.1007/s10822-010-9338-4
More informationFROM MOLECULAR FORMULAS TO MARKUSH STRUCTURES
FROM MOLECULAR FORMULAS TO MARKUSH STRUCTURES DIFFERENT LEVELS OF KNOWLEDGE REPRESENTATION IN CHEMISTRY Michael Braden, PhD ACS / San Diego/ 2016 Overview ChemAxon Who are we? Examples/use cases: Create
More informationMolecular Complexity Effects and Fingerprint-Based Similarity Search Strategies
Molecular Complexity Effects and Fingerprint-Based Similarity Search Strategies Dissertation zur Erlangung des Doktorgrades (Dr. rer. nat.) der Mathematisch-aturwissenschaftlichen Fakultät der Rheinischen
More informationChemical Space. Space, Diversity, and Synthesis. Jeremy Henle, 4/23/2013
Chemical Space Space, Diversity, and Synthesis Jeremy Henle, 4/23/2013 Computational Modeling Chemical Space As a diversity construct Outline Quantifying Diversity Diversity Oriented Synthesis Wolf and
More informationDOCKING TUTORIAL. A. The docking Workflow
2 nd Strasbourg Summer School on Chemoinformatics VVF Obernai, France, 20-24 June 2010 E. Kellenberger DOCKING TUTORIAL A. The docking Workflow 1. Ligand preparation It consists in the standardization
More informationThe Schrödinger KNIME extensions
The Schrödinger KNIME extensions Computational Chemistry and Cheminformatics in a workflow environment Jean-Christophe Mozziconacci Volker Eyrich KNIME UGM, Zurich, February 2014 The Schrödinger extensions
More informationRetrieving hits through in silico screening and expert assessment M. N. Drwal a,b and R. Griffith a
Retrieving hits through in silico screening and expert assessment M.. Drwal a,b and R. Griffith a a: School of Medical Sciences/Pharmacology, USW, Sydney, Australia b: Charité Berlin, Germany Abstract:
More informationVirtual screening in drug discovery
Virtual screening in drug discovery Pavel Polishchuk Institute of Molecular and Translational Medicine Palacky University pavlo.polishchuk@upol.cz Drug development workflow Vistoli G., et al., Drug Discovery
More informationChemoinformatics and Drug Discovery
Molecules 2002, 7, 566-600 molecules ISSN 1420-3049 http://www.mdpi.org Review: Chemoinformatics and Drug Discovery Jun Xu* and Arnold Hagler Discovery Partners International, Inc., 9640 Towne Center Drive,
More informationMerck Virtual Library (MVL): Deployment, Application, and Future Enhancement
Merck Virtual Library (MVL): Deployment, Application, and Future Enhancement Zhengwei Peng Informatics, Discovery Chemistry, Merck & Co., Inc., Kenilworth, NJ, USA, and ChemAxon UGM, Boston, MA, USA Contents
More informationESPRESSO (Extremely Speedy PRE-Screening method with Segmented compounds) 1
Vol.2016-MPS-108 o.18 Vol.2016-BI-46 o.18 ESPRESS 1,4,a) 2,4 2,4 1,3 1,3,4 1,3,4 - ESPRESS (Extremely Speedy PRE-Screening method with Segmented cmpounds) 1 Glide HTVS ESPRESS 2,900 200 ESPRESS: An ultrafast
More informationDesign and Synthesis of the Comprehensive Fragment Library
YOUR INNOVATIVE CHEMISTRY PARTNER IN DRUG DISCOVERY Design and Synthesis of the Comprehensive Fragment Library A 3D Enabled Library for Medicinal Chemistry Discovery Warren S Wade 1, Kuei-Lin Chang 1,
More informationTargeting protein-protein interactions: A hot topic in drug discovery
Michal Kamenicky; Maria Bräuer; Katrin Volk; Kamil Ödner; Christian Klein; Norbert Müller Targeting protein-protein interactions: A hot topic in drug discovery 104 Biomedizin Innovativ patientinnenfokussierte,
More informationIgnasi Belda, PhD CEO. HPC Advisory Council Spain Conference 2015
Ignasi Belda, PhD CEO HPC Advisory Council Spain Conference 2015 Business lines Molecular Modeling Services We carry out computational chemistry projects using our selfdeveloped and third party technologies
More informationCheminformatics analysis and learning in a data pipelining environment
Molecular Diversity (2006) 10: 283 299 DOI: 10.1007/s11030-006-9041-5 c Springer 2006 Review Cheminformatics analysis and learning in a data pipelining environment Moises Hassan 1,, Robert D. Brown 1,
More informationPerforming a Pharmacophore Search using CSD-CrossMiner
Table of Contents Introduction... 2 CSD-CrossMiner Terminology... 2 Overview of CSD-CrossMiner... 3 Searching with a Pharmacophore... 4 Performing a Pharmacophore Search using CSD-CrossMiner Version 2.0
More informationHow to Create a Substance Answer Set
How to Create a Substance Answer Set Select among five search techniques to find substances Since substances can be described by multiple names or other characteristics, SciFinder gives you the flexibility
More informationBridging the Dimensions:
Bridging the Dimensions: Seamless Integration of 3D Structure-based Design and 2D Structure-activity Relationships to Guide Medicinal Chemistry ACS Spring National Meeting. COMP, March 13 th 2016 Marcus
More informationDocking. GBCB 5874: Problem Solving in GBCB
Docking Benzamidine Docking to Trypsin Relationship to Drug Design Ligand-based design QSAR Pharmacophore modeling Can be done without 3-D structure of protein Receptor/Structure-based design Molecular
More informationRapid Application Development using InforSense Open Workflow and Daylight Technologies Deliver Discovery Value
Rapid Application Development using InforSense Open Workflow and Daylight Technologies Deliver Discovery Value Anthony Arvanites Daylight User Group Meeting March 10, 2005 Outline 1. Company Introduction
More informationHow Diverse Are Diversity Assessment Methods? A Comparative Analysis and Benchmarking of Molecular Descriptor Space
pubs.acs.org/jcim How Diverse Are Diversity Assessment Methods? A Comparative Analysis and Benchmarking of Molecular Descriptor Space Alexios Koutsoukas,, Shardul Paricharak,,, Warren R. J. D. Galloway,
More informationÁkos Tarcsay CHEMAXON SOLUTIONS
Ákos Tarcsay CHEMAXON SOLUTIONS FINDING NOVEL COMPOUNDS WITH IMPROVED OVERALL PROPERTY PROFILES Two faces of one world Structure Footprint Linked Data Reactions Analytical Batch Phys-Chem Assay Project
More informationMedicinal Chemistry/ CHEM 458/658 Chapter 4- Computer-Aided Drug Design
Medicinal Chemistry/ CHEM 458/658 Chapter 4- Computer-Aided Drug Design Bela Torok Department of Chemistry University of Massachusetts Boston Boston, MA 1 Computer Aided Drug Design - Introduction Development
More informationPose and affinity prediction by ICM in D3R GC3. Max Totrov Molsoft
Pose and affinity prediction by ICM in D3R GC3 Max Totrov Molsoft Pose prediction method: ICM-dock ICM-dock: - pre-sampling of ligand conformers - multiple trajectory Monte-Carlo with gradient minimization
More informationCross Discipline Analysis made possible with Data Pipelining. J.R. Tozer SciTegic
Cross Discipline Analysis made possible with Data Pipelining J.R. Tozer SciTegic System Genesis Pipelining tool created to automate data processing in cheminformatics Modular system built with generic
More informationEarly Stages of Drug Discovery in the Pharmaceutical Industry
Early Stages of Drug Discovery in the Pharmaceutical Industry Daniel Seeliger / Jan Kriegl, Discovery Research, Boehringer Ingelheim September 29, 2016 Historical Drug Discovery From Accidential Discovery
More informationAMRI COMPOUND LIBRARY CONSORTIUM: A NOVEL WAY TO FILL YOUR DRUG PIPELINE
AMRI COMPOUD LIBRARY COSORTIUM: A OVEL WAY TO FILL YOUR DRUG PIPELIE Muralikrishna Valluri, PhD & Douglas B. Kitchen, PhD Summary The creation of high-quality, innovative small molecule leads is a continual
More informationbcl::cheminfo Suite Enables Machine Learning-Based Drug Discovery Using GPUs Edward W. Lowe, Jr. Nils Woetzel May 17, 2012
bcl::cheminfo Suite Enables Machine Learning-Based Drug Discovery Using GPUs Edward W. Lowe, Jr. Nils Woetzel May 17, 2012 Outline Machine Learning Cheminformatics Framework QSPR logp QSAR mglur 5 CYP
More informationSimilarity methods for ligandbased virtual screening
Similarity methods for ligandbased virtual screening Peter Willett, University of Sheffield Computers in Scientific Discovery 5, 22 nd July 2010 Overview Molecular similarity and its use in virtual screening
More informationGCC E x h i b i t i o n N e w s l e t t e r. 8 th GERMAN CONFERENCE ON CHEMOINFORMATICS TOPICS
TOPICS GCC 2012 8 th GERMAN CONFERENCE ON CHEMOINFORMATICS E x h i b i t i o n N e w s l e t t e r List of Exhibitors Pre-Conference Workshops Free Software Session Room Plans Exhibitor One-Pagers www.gdch.de/gcc2012
More informationMolecular Modelling. Computational Chemistry Demystified. RSC Publishing. Interprobe Chemical Services, Lenzie, Kirkintilloch, Glasgow, UK
Molecular Modelling Computational Chemistry Demystified Peter Bladon Interprobe Chemical Services, Lenzie, Kirkintilloch, Glasgow, UK John E. Gorton Gorton Systems, Glasgow, UK Robert B. Hammond Institute
More informationData Quality Issues That Can Impact Drug Discovery
Data Quality Issues That Can Impact Drug Discovery Sean Ekins 1, Joe Olechno 2 Antony J. Williams 3 1 Collaborations in Chemistry, Fuquay Varina, NC. 2 Labcyte Inc, Sunnyvale, CA. 3 Royal Society of Chemistry,
More informationGyörgy M. Keserű H2020 FRAGNET Network Hungarian Academy of Sciences
Fragment based lead discovery - introduction György M. Keserű H2020 FRAGET etwork Hungarian Academy of Sciences www.fragnet.eu Hit discovery from screening Druglike library Fragment library Large molecules
More informationBioinformatics Workshop - NM-AIST
Bioinformatics Workshop - NM-AIST Day 3 Introduction to Drug/Small Molecule Discovery Thomas Girke July 25, 2012 Bioinformatics Workshop - NM-AIST Slide 1/44 Introduction CMP Structure Formats Similarity
More informationDifferent conformations of the drugs within the virtual library of FDA approved drugs will be generated.
Chapter 3 Molecular Modeling 3.1. Introduction In this study pharmacophore models will be created to screen a virtual library of FDA approved drugs for compounds that may inhibit MA-A and MA-B. The virtual
More informationHit Finding and Optimization Using BLAZE & FORGE
Hit Finding and Optimization Using BLAZE & FORGE Kevin Cusack,* Maria Argiriadi, Eric Breinlinger, Jeremy Edmunds, Michael Hoemann, Michael Friedman, Sami Osman, Raymond Huntley, Thomas Vargo AbbVie, Immunology
More informationWeb tools for Monomer selection, Library Design and Compound Acquisition. Andrew Leach GlaxoSmithKline Research and Development Stevenage
Web tools for Monomer selection, Library Design and Compound Acquisition Andrew Leach GlaxoSmithKline Research and Development Stevenage Historical perspective Bench scientists unused to dealing with and
More informationEMPIRICAL VS. RATIONAL METHODS OF DISCOVERING NEW DRUGS
EMPIRICAL VS. RATIONAL METHODS OF DISCOVERING NEW DRUGS PETER GUND Pharmacopeia Inc., CN 5350 Princeton, NJ 08543, USA pgund@pharmacop.com Empirical and theoretical approaches to drug discovery have often
More informationAnalyzing Small Molecule Data in R
Analyzing Small Molecule Data in R Tyler Backman and Thomas Girke December 12, 2011 Analyzing Small Molecule Data in R Slide 1/49 Introduction CMP Structure Formats Similarity Searching Background Fragment
More informationReaxys The Highlights
Reaxys The Highlights What is Reaxys? A brand new workflow solution for research chemists and scientists from related disciplines An extensive repository of reaction and substance property data A resource
More informationOctober 6 University Faculty of pharmacy Computer Aided Drug Design Unit
October 6 University Faculty of pharmacy Computer Aided Drug Design Unit CADD@O6U.edu.eg CADD Computer-Aided Drug Design Unit The development of new drugs is no longer a process of trial and error or strokes
More informationIdentifying Interaction Hot Spots with SuperStar
Identifying Interaction Hot Spots with SuperStar Version 1.0 November 2017 Table of Contents Identifying Interaction Hot Spots with SuperStar... 2 Case Study... 3 Introduction... 3 Generate SuperStar Maps
More informationVirtual Screening: How Are We Doing?
Virtual Screening: How Are We Doing? Mark E. Snow, James Dunbar, Lakshmi Narasimhan, Jack A. Bikker, Dan Ortwine, Christopher Whitehead, Yiannis Kaznessis, Dave Moreland, Christine Humblet Pfizer Global
More informationStructure-Activity Modeling - QSAR. Uwe Koch
Structure-Activity Modeling - QSAR Uwe Koch QSAR Assumption: QSAR attempts to quantify the relationship between activity and molecular strcucture by correlating descriptors with properties Biological activity
More information