LEADER 05529nam 2200685Ia 450 001 9910146240603321 005 20170809173127.0 010 $a1-280-52057-4 010 $a9786610520572 010 $a3-527-60551-7 010 $a3-527-60181-3 035 $a(CKB)1000000000019340 035 $a(EBL)481427 035 $a(OCoLC)68963317 035 $a(SSID)ssj0000229648 035 $a(PQKBManifestationID)11203518 035 $a(PQKBTitleCode)TC0000229648 035 $a(PQKBWorkID)10187721 035 $a(PQKB)11663501 035 $a(MiAaPQ)EBC481427 035 $a(iGPub)WILEYB0031791 035 $a(EXLCZ)991000000000019340 100 $a20030110d2003 uy 0 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt 182 $cc 183 $acr 200 00$aProtein-ligand interactions from molecular recognition to drug design$b[electronic resource] /$fedited by H.-J. Bo?hm and G. Schneider 205 $a1st ed. 210 $aWeinheim $cCambridge $cWiley-VCH$d2003 215 $a1 online resource (264 p.) 225 1 $aMethods and Principles in Medicinal Chemistry ;$vv.27 300 $aDescription based upon print version of record. 311 $a3-527-30521-1 327 $aProtein-Ligand Interactions From Molecular Recognition to Drug Design; Contents; Preface; A Personal Foreword; List of Contributors; List of Abbreviations; Prologue; 1 Prediction of Non-bonded Interactions in Drug Design; 1.1 Introduction; 1.2 Major Contributions to Protein-Ligand Interactions; 1.3 Description of Scoring Functions for Receptor-Ligand Interactions; 1.3.1 Force Field-based Methods; 1.3.2 Empirical Scoring Functions; 1.3.3 Knowledge-based Methods; 1.4 Some Limitations of Current Scoring Functions; 1.4.1 Influence of the Training Data; 1.4.2 Molecular Size 327 $a1.4.3 Water Structure and Protonation State1.5 Application of Scoring Functions in Virtual Screening and De Novo Design; 1.5.1 Successful Identification of Novel Leads Through Virtual Screening; 1.5.2 De novo Ligand Design with LUDI; 1.6 Outlook; 1.7 Acknowledgments; 1.8 References; 2 Introduction to Molecular Recognition Models; 2.1 Introduction and Scope; 2.2 Additivity of Pairwise Interactions - The Chelate Effect; 2.3 Geometric Fitting: The Hole-size Concept; 2.4 Di- and Polytopic Interactions: Change of Binding Mechanism with Different Fit; 2.5 Deviations from the Lock-and-Key Principle 327 $a2.5.1 Strain in Host-Guest Complexes2.5.2 Solvent Effects; 2.5.3 Enthalpy/Entropy Variations; 2.5.4 Loose Fit in Hydrophobically Driven Complex Formation; 2.6 Conformational Pre-organization: Flexible vs. Rigid Hosts; 2.7 Selectivity and Stability in Supramolecular Complexes; 2.8 Induced Fit, Cooperativity, and Allosteric Effects; 2.9 Quantification of Non-covalent Forces; 2.9.1 Ion Pairs and Electrostatic Donor-Acceptor Interactions; 2.9.2 Hydrogen Bonds; 2.9.3 Weak Hydrogen Bonds: The Use of Intramolecular ""Balances"; 2.9.4 Polarization Effects; 2.9.5 Dispersive Interactions 327 $a2.10 Conclusions2.11 References; 3 Experimental Approaches to Determine the Thermodynamics of Protein-Ligand Interactions; 3.1 Introduction; 3.2 Basic Thermodynamics of Protein-Ligand Interactions; 3.3 Measurement of Thermodynamic Parameters; 3.3.1 Calorimetric Determination of Thermodynamic Parameters; 3.3.2 van't Hoff Determination of Thermodynamic Parameters; 3.3.2.1 Relationship to Equilibrium Constant; 3.3.2.2 Obtaining the Equilibrium Constant; 3.4 Applications; 3.4.1 Calorimetric Determination of Thermodynamic Parameters; 3.4.2 van't Hoff Determination of Thermodynamic Parameters 327 $a3.5 Caveats3.6 Summary; 3.7 References; 4 The Biophore Concept; 4.1 Introduction; 4.2 Methodology for Pharmacophore Detection and Searching; 4.2.1 Definition of Pharmacophoric Groups; 4.2.2 Ligand-based Methods for Pharmacophore Perception; 4.2.3 Protein Structure-based Pharmacophore Perception; 4.2.4 Methods for Pharmacophore Searching; 4.3 Pharmacophore Fingerprints; 4.4 Applications of the Biophore Concept; 4.4.1 Lead Generation; 4.4.2 Multi-pharmacophore Descriptors in Diversity Analysis and Library Design; 4.4.3 Structure-based Design; 4.5 The Biophore Concept in ADME Prediction 327 $a4.6 Summary 330 $aThe lock-and-key principle formulated by Emil Fischer as early as the end of the 19th century has still not lost any of its significance for the life sciences. The basic aspects of ligand-protein interaction may be summarized under the term 'molecular recognition' and concern the specificity as well as stability of ligand binding. Molecular recognition is thus a central topic in the development of active substances, since stability and specificity determine whether a substance can be used as a drug. Nowadays, computer-aided prediction and intelligent molecular design make a large contributio 410 0$aMethods and Principles in Medicinal Chemistry 606 $aLigand binding (Biochemistry) 606 $aBiochemistry 608 $aElectronic books. 615 0$aLigand binding (Biochemistry) 615 0$aBiochemistry. 676 $a572.33 676 $a615.19 676 $a615/.19 701 $aBo?hm$b Hans-Joachim$0902275 701 $aSchneider$b Gisbert$f1965-$0855861 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910146240603321 996 $aProtein-ligand interactions from molecular recognition to drug design$92183924 997 $aUNINA