LEADER 08965nam 22016573u 450 001 9910840589803321 005 20230124182326.0 010 $a1-280-85421-9 010 $a9786610854219 010 $a3-527-60767-6 010 $a3-527-60713-7 035 $a(CKB)1000000000376649 035 $a(EBL)481388 035 $a(SSID)ssj0000204885 035 $a(PQKBManifestationID)11189249 035 $a(PQKBTitleCode)TC0000204885 035 $a(PQKBWorkID)10208886 035 $a(PQKB)10837468 035 $a(MiAaPQ)EBC481388 035 $a(OCoLC)85821170 035 $a(EXLCZ)991000000000376649 100 $a20131104d2006|||| u|| | 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt 182 $cc 183 $acr 200 10$aMolecular Interaction Fields$b[electronic resource] $eApplications in Drug Discovery and ADME Prediction 210 $aHoboken $cWiley$d2006 215 $a1 online resource (323 p.) 225 1 $aMethods and Principles in Medicinal Chemistry ;$vv.33 300 $aDescription based upon print version of record. 311 $a3-527-31087-8 327 $aMolecular Interaction Fields; A Personal Foreword; Contents; Preface; List of Contributors; I Introduction; 1 The Basic Principles of GRID; 1.1 Introduction; 1.2 Philosophy and Objectives; 1.3 Priorities; 1.4 The GRID Method; 1.4.1 GRID Probes Are Anisometric; 1.4.2 The Target "Responds" to the Probe; 1.4.3 The Target is Immersed in Water; 1.5 The GRID Force Field; 1.5.1 The Lennard-Jones Term; 1.5.2 The Electrostatic Term; 1.5.3 The Hydrogen Bond Term; 1.5.4 The Other Terms; 1.6 Nomenclature; 1.6.1 "ATOM" Records; 1.6.2 "HETATM" Records; 1.7 Calibrating the GRID Force Field 327 $a1.7.1 Checking the Calibration1.7.2 Checking Datafile GRUB; 1.8 The Output from GRID; 1.8.1 GRID Maps from Macromolecules; 1.8.2 GRID Maps from a Small Molecule; 1.9 Conclusions; 2 Calculation and Application of Molecular Interaction Fields; 2.1 Introduction; 2.2 Calculation of MIFs; 2.2.1 The Target; 2.2.2 The Probe; 2.2.3 The Interaction Function; 2.2.3.1 Van der Waals Interactions; 2.2.3.2 Electrostatic Interactions; 2.2.3.3 Hydrogen Bonds; 2.2.3.4 Entropy; 2.3 Selected Applications of MIFs; 2.3.1 Mapping a Ligand Binding Site in a Protein; 2.3.2 Deriving 3D-QSARs 327 $a2.3.3 Similarity Analysis of a Set of Related Molecules2.4 Concluding Remarks and Outlook; II Pharmacodynamics; 3 Protein Selectivity Studies Using GRID-MIFs; 3.1 Introduction; 3.2 GRID Calculations and Chemometric Analysis; 3.2.1 Source and Selection of Target Structures; 3.2.2 Selection and Superimposition of Binding Sites; 3.2.3 Calculation of the Molecular Interaction Field; 3.2.4 Matrix Generation and Pretreatments; 3.2.4.1 Region Cut-outs; 3.2.5 GRID/PCA; 3.2.5.1 Score Plots; 3.2.5.2 Two-Dimensional Loading Plots; 3.2.5.3 Loading Contour Maps; 3.2.5.4 Problems of GRID/PCA 327 $a3.2.6 GRID/CPCA3.2.6.1 Block Unscaled Weights; 3.2.6.2 CPCA; 3.2.6.3 Identification of Important Variable Blocks for Selectivity; 3.2.6.4 Contour Plots; 3.3 Applications; 3.3.1 DNA Minor Groove Binding - Compare AAA and GGG Double Helix; 3.3.2 Dihydrofolate Reductase; 3.3.3 Cyclooxygenase; 3.3.4 Penicillin Acylase; 3.3.5 Serine Proteases; 3.3.5.1 S1 Pocket; 3.3.5.2 P Pocket; 3.3.5.3 D Pocket; 3.3.6 CYP450; 3.3.7 Target Family Landscapes of Protein Kinases; 3.3.8 Matrix Metalloproteinases (MMPs); 3.3.9 Nitric Oxide Synthases; 3.3.10 PPARs; 3.3.11 Bile Acid Transportation System 327 $a3.3.12 Ephrin Ligands and Eph Kinases3.4 Discussion and Conclusion; 4 FLAP: 4-Point Pharmacophore Fingerprints from GRID; 4.1 Introduction; 4.1.1 Pharmacophores and Pharmacophore Fingerprints; 4.1.2 FLAP; 4.2 FLAP Theory; 4.3 Docking; 4.3.1 GLUE: A New Docking Program Based on Pharmacophores; 4.3.2 Case Study; 4.4 Structure Based Virtual Screening (SBVS); 4.5 Ligand Based Virtual Screening (LBVS); 4.6 Protein Similarity; 4.7 TOPP (Triplets of Pharmacophoric Points); 4.8 Conclusions; 5 The Complexity of Molecular Interaction: Molecular Shape Fingerprints by the PathFinder Approach 327 $a5.1 Introduction 330 $aThis unique reference source, edited by the world's most respected expert on molecular interaction field software, covers all relevant principles of the GRID force field and its applications in medicinal chemistry. Entire chapters on 3D-QSAR, pharmacophore searches, docking studies, metabolism predictions and protein selectivity studies, among others, offer a concise overview of this emerging field. As an added bonus, this handbook includes a CD-ROM with the latest commercial versions of the GRID program and related software. 410 0$aMethods and Principles in Medicinal Chemistry 606 $aBiomolecules 606 $aChemical reactions -- Computer simulation 606 $aChemicals -- Pharmacokinetics -- Forecasting 606 $aChemicals -- Physiological effect -- Forecasting 606 $aDrug development 606 $aPharmaceutical chemistry 606 $aStructure-activity relationships (Biochemistry) -- Computer simulation 606 $aPharmaceutical chemistry$xPhysiological effect$xForecasting 606 $aChemicals$xComputer simulation 606 $aChemical reactions$xComputer simulation 606 $aDrug development 606 $aStructure-activity relationships (Biochemistry) 606 $aBiomolecules 606 $aComputational Biology 606 $aModels, Molecular 606 $aQuantitative Structure-Activity Relationship 606 $aComputer Simulation 606 $aDrug Design 606 $aPharmaceutical Preparations 606 $aSoftware 606 $aStructure-Activity Relationship 606 $aBiology 606 $aDrug Discovery 606 $aComputing Methodologies 606 $aChemicals and Drugs 606 $aModels, Theoretical 606 $aBiological Science Disciplines 606 $aChemistry, Pharmaceutical 606 $aBiochemical Phenomena 606 $aInformation Science 606 $aPharmacological Phenomena 606 $aInvestigative Techniques 606 $aNatural Science Disciplines 606 $aAnalytical, Diagnostic and Therapeutic Techniques and Equipment 606 $aPharmacology 606 $aPhysiological Phenomena 606 $aChemistry 606 $aChemical Phenomena 606 $aPhenomena and Processes 606 $aDisciplines and Occupations 606 $aPharmacy, Therapeutics, & Pharmacology$2HILCC 606 $aHistory of Medicine$2HILCC 606 $aHealth & Biological Sciences$2HILCC 606 $aMedicine$2HILCC 615 4$aBiomolecules. 615 4$aChemical reactions -- Computer simulation. 615 4$aChemicals -- Pharmacokinetics -- Forecasting. 615 4$aChemicals -- Physiological effect -- Forecasting. 615 4$aDrug development. 615 4$aPharmaceutical chemistry. 615 4$aStructure-activity relationships (Biochemistry) -- Computer simulation. 615 0$aPharmaceutical chemistry$xPhysiological effect$xForecasting 615 0$aChemicals$xComputer simulation 615 0$aChemical reactions$xComputer simulation 615 0$aDrug development 615 0$aStructure-activity relationships (Biochemistry) 615 0$aBiomolecules 615 2$aComputational Biology 615 2$aModels, Molecular 615 2$aQuantitative Structure-Activity Relationship 615 2$aComputer Simulation 615 2$aDrug Design 615 2$aPharmaceutical Preparations 615 2$aSoftware 615 2$aStructure-Activity Relationship 615 2$aBiology 615 2$aDrug Discovery 615 2$aComputing Methodologies 615 2$aChemicals and Drugs 615 2$aModels, Theoretical 615 2$aBiological Science Disciplines 615 2$aChemistry, Pharmaceutical 615 2$aBiochemical Phenomena 615 2$aInformation Science 615 2$aPharmacological Phenomena 615 2$aInvestigative Techniques 615 2$aNatural Science Disciplines 615 2$aAnalytical, Diagnostic and Therapeutic Techniques and Equipment 615 2$aPharmacology 615 2$aPhysiological Phenomena 615 2$aChemistry 615 2$aChemical Phenomena 615 2$aPhenomena and Processes 615 2$aDisciplines and Occupations 615 7$aPharmacy, Therapeutics, & Pharmacology 615 7$aHistory of Medicine 615 7$aHealth & Biological Sciences 615 7$aMedicine 676 $a615.19 700 $aCruciani$b Gabriele$01727431 701 $aMannhold$b Raimund$0924942 701 $aKubinyi$b Hugo$096070 701 $aFolkers$b Gerd$0505529 801 0$bAU-PeEL 801 1$bAU-PeEL 801 2$bAU-PeEL 906 $aBOOK 912 $a9910840589803321 996 $aMolecular Interaction Fields$94134524 997 $aUNINA