LEADER 05354nam 22006614a 450 001 9910145814603321 005 20200520144314.0 010 $a1-282-26783-3 010 $a9786612267833 010 $a0-470-45185-8 010 $a0-470-45184-X 035 $a(CKB)1000000000715904 035 $a(EBL)416234 035 $a(OCoLC)476247297 035 $a(SSID)ssj0000127579 035 $a(PQKBManifestationID)11147624 035 $a(PQKBTitleCode)TC0000127579 035 $a(PQKBWorkID)10052992 035 $a(PQKB)11625150 035 $a(MiAaPQ)EBC416234 035 $a(Au-PeEL)EBL416234 035 $a(CaPaEBR)ebr10297805 035 $a(CaONFJC)MIL226783 035 $a(PPN)243326491 035 $a(OCoLC)977486001 035 $a(FINmELB)ELB178990 035 $a(EXLCZ)991000000000715904 100 $a20080923d2009 uy 0 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt$2rdacontent 182 $cc$2rdamedia 183 $acr$2rdacarrier 200 10$aComputational drug design $ea guide for computational and medicinal chemists /$fDavid C. Young 205 $a1st ed. 210 $aHoboken, N.J. $cJohn Wiley & Sons$dc2009 215 $a1 online resource (xxxvi, 307 pages) $cillustrations 311 0 $a0-470-12685-X 320 $aIncludes bibliographical references and index. 327 $aCOMPUTATIONAL DRUG DESIGN; CONTENTS; PREFACE; ACKNOWLEDGMENTS; ABOUT THE AUTHOR; SYMBOLS USED IN THIS BOOK; BOOK ABSTRACT; 1 Introduction; 1.1 A Difficult Problem; 1.2 An Expensive Problem; 1.3 Where Computational Techniques are Used; Bibliography; PART I THE DRUG DESIGN PROCESS; 2 Properties that Make a Molecule a Good Drug; 2.1 Compound Testing; 2.1.1 Biochemical Assays; 2.1.2 Cell-Based Assays; 2.1.3 Animal Testing; 2.1.4 Human Clinical Trials; 2.2 Molecular Structure; 2.2.1 Activity; 2.2.2 Bioavailability and Toxicity; 2.2.3 Drug Side Effects; 2.2.4 Multiple Drug Interactions 327 $a2.3 Metrics for Drug-Likeness; 2.4 Exceptions to the Rules; Bibliography; 3 Target Identification; 3.1 Primary Sequence and Metabolic Pathway; 3.2 Crystallography; 3.3 2D NMR; 3.4 Homology Models; 3.5 Protein Folding; Bibliography; 4 Target Characterization; 4.1 Analysis of Target Mechanism; 4.1.1 Kinetics and Crystallography; 4.1.2 Automated Crevice Detection; 4.1.3 Transition Structures and Reaction Coordinates; 4.1.4 Molecular Dynamics Simulations; 4.2 Where the Target is Expressed; 4.3 Pharmacophore Identification; 4.4 Choosing an Inhibitor Mechanism; Bibliography 327 $a5 The Drug Design Process for a Known Protein Target; 5.1 The Structure-Based Design Process; 5.2 Initial Hits; 5.3 Compound Refinement; 5.4 ADMET; 5.5 Drug Resistance; Bibliography; 6 The Drug Design Process for an Unknown Target; 6.1 The Ligand-Based Design Process; 6.2 Initial Hits; 6.3 Compound Refinement; 6.4 ADMET; Bibliography; 7 Drug Design for Other Targets; 7.1 DNA Binding; 7.2 RNA as a Target; 7.3 Allosteric Sites; 7.4 Receptor Targets; 7.5 Steroids; 7.6 Targets inside Cells; 7.7 Targets within the Central Nervous System; 7.8 Irreversibly Binding Inhibitors 327 $a7.9 Upregulating Target Activity; Bibliography; 8 Compound Library Design; 8.1 Targeted Libraries versus Diverse Libraries; 8.2 From Fragments versus from Reactions; 8.3 Non-Enumerative Techniques; 8.4 Drug-Likeness and Synthetic Accessibility; 8.5 Analyzing Chemical Diversity and Spanning known Chemistries; 8.6 Compound Selection Techniques; Bibliography; PART II COMPUTATIONAL TOOLS AND TECHNIQUES; 9 Homology Model Building; 9.1 How much Similarity is Enough?; 9.2 Steps for Building a Homology Model; 9.2.1 Step 1: Template Identification 327 $a9.2.2 Step 2: Alignment between the Unknown and the Template; 9.2.3 Step 3: Manual Adjustments to the Alignment; 9.2.4 Step 4: Replace Template Side Chains with Model Side Chains; 9.2.5 Step 5: Adjust Model for Insertions and Deletions; 9.2.6 Step 6: Optimization of the Model; 9.2.7 Step 7: Model Validation; 9.2.8 Step 8: If Errors are Found, Iterate Back to Previous Steps; 9.3 Reliability of Results; Bibliography; 10 Molecular Mechanics; 10.1 A Really Brief Introduction to Molecular Mechanics; 10.2 Force Fields for Drug Design; Bibliography; 11 Protein Folding; 11.1 The Difficulty of the Problem 330 $aHelps you choose the right computational tools and techniques to meet your drug design goals Computational Drug Design covers all of the major computational drug design techniques in use today, focusing on the process that pharmaceutical chemists employ to design a new drug molecule. The discussions of which computational tools to use and when and how to use them are all based on typical pharmaceutical industry drug design processes. Following an introduction, the book is divided into three parts: Part One, The Drug Design Process, sets forth a variety of design processes 606 $aDrugs$xDesign$xMathematical models 606 $aDrugs$xDesign$xData processing 615 0$aDrugs$xDesign$xMathematical models. 615 0$aDrugs$xDesign$xData processing. 676 $a615/.190285 700 $aYoung$b David C.$f1964-$0514308 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910145814603321 996 $aComputational Drug Design$9852152 997 $aUNINA