08965nam 22016573u 450 991084058980332120230124182326.01-280-85421-997866108542193-527-60767-63-527-60713-7(CKB)1000000000376649(EBL)481388(SSID)ssj0000204885(PQKBManifestationID)11189249(PQKBTitleCode)TC0000204885(PQKBWorkID)10208886(PQKB)10837468(MiAaPQ)EBC481388(OCoLC)85821170(EXLCZ)99100000000037664920131104d2006|||| u|| |engur|n|---|||||txtccrMolecular Interaction Fields[electronic resource] Applications in Drug Discovery and ADME PredictionHoboken Wiley20061 online resource (323 p.)Methods and Principles in Medicinal Chemistry ;v.33Description based upon print version of record.3-527-31087-8 Molecular 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 Field1.7.1 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-QSARs2.3.3 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/PCA3.2.6 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 System3.3.12 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 Approach5.1 IntroductionThis 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.Methods and Principles in Medicinal ChemistryBiomoleculesChemical reactions -- Computer simulationChemicals -- Pharmacokinetics -- ForecastingChemicals -- Physiological effect -- ForecastingDrug developmentPharmaceutical chemistryStructure-activity relationships (Biochemistry) -- Computer simulationPharmaceutical chemistryPhysiological effectForecastingChemicalsComputer simulationChemical reactionsComputer simulationDrug developmentStructure-activity relationships (Biochemistry)BiomoleculesComputational BiologyModels, MolecularQuantitative Structure-Activity RelationshipComputer SimulationDrug DesignPharmaceutical PreparationsSoftwareStructure-Activity RelationshipBiologyDrug DiscoveryComputing MethodologiesChemicals and DrugsModels, TheoreticalBiological Science DisciplinesChemistry, PharmaceuticalBiochemical PhenomenaInformation SciencePharmacological PhenomenaInvestigative TechniquesNatural Science DisciplinesAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPharmacologyPhysiological PhenomenaChemistryChemical PhenomenaPhenomena and ProcessesDisciplines and OccupationsPharmacy, Therapeutics, & PharmacologyHILCCHistory of MedicineHILCCHealth & Biological SciencesHILCCMedicineHILCCBiomolecules.Chemical reactions -- Computer simulation.Chemicals -- Pharmacokinetics -- Forecasting.Chemicals -- Physiological effect -- Forecasting.Drug development.Pharmaceutical chemistry.Structure-activity relationships (Biochemistry) -- Computer simulation.Pharmaceutical chemistryPhysiological effectForecastingChemicalsComputer simulationChemical reactionsComputer simulationDrug developmentStructure-activity relationships (Biochemistry)BiomoleculesComputational BiologyModels, MolecularQuantitative Structure-Activity RelationshipComputer SimulationDrug DesignPharmaceutical PreparationsSoftwareStructure-Activity RelationshipBiologyDrug DiscoveryComputing MethodologiesChemicals and DrugsModels, TheoreticalBiological Science DisciplinesChemistry, PharmaceuticalBiochemical PhenomenaInformation SciencePharmacological PhenomenaInvestigative TechniquesNatural Science DisciplinesAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPharmacologyPhysiological PhenomenaChemistryChemical PhenomenaPhenomena and ProcessesDisciplines and OccupationsPharmacy, Therapeutics, & PharmacologyHistory of MedicineHealth & Biological SciencesMedicine615.19Cruciani Gabriele1727431Mannhold Raimund924942Kubinyi Hugo96070Folkers Gerd505529AU-PeELAU-PeELAU-PeELBOOK9910840589803321Molecular Interaction Fields4134524UNINA