QUANTUM MEDICINAL CHEMISTRY

By KENNETH ROBINSON

QM/MM APPROACHES AB INITIO METHODS IN THE STUDY OF REACTION MECHANISMS – THEIR ROLE AND PERSPECTIVES IN MEDICINAL CHEMISTRY INTRODUCTION METHODS HYBRID QM/MM POTENTIAL QM/MM BOUNDARY – THE LINK ATOM APPROACH QM/MM BOUNDARY – THE HYBRID ORBITAL APPROACH THERMODYNAMICALLY COUPLED QM/MM SELECTED APPLICATIONS OF QM/MM METHODS URACIL-DNA GLYCOSYLASE QM/MM SIMULATIONS OF QUANTUM EFFECTS MISCELLANEOUS APPLICATIONS CONCLUSIONS REFERENCES QUANTUM-MECHANICAL/MOLECULAR-MECHANICAL METHODS IN MEDICINAL CHEMISTRY THEORY METHODOLOGY BASIC THEORY QM/MM PARTITIONING SCHEMES PRACTICAL ASPECTS OF MODELING ENZYME REACTIONS CHOICE AND PREPARATION OF THE STARTING STRUCTURE DEFINITION OF THE QM REGION CHOICE OF THE QM METHOD TECHNIQUES FOR REACTION MODELING OPTIMIZATION OF TRANSITION STRUCTURES AND REACTION PATHWAYS DYNAMICS AND FREE ENERGY CALCULATIONS SOME RECENT APPLICATIONS HUMAN ALDOSE REDUCTASE GLUTATHIONE S-TRANSFERASES INFLUENZA NEURAMINIDASE HUMAN THROMBIN HUMAN IMMUNODEFICIENCY VIRUS PROTEASE MOLECULAR PROPERTIES ATOMS IN MEDICINAL CHEMISTRY WHY DEFINE ATOMS IN MOLECULES? THEORY OF ATOMS IN MOLECULES DEFINITION OF ATOMS AND MOLECULAR STRUCTURE DEFINITION OF ATOMIC PROPERTIES ATOMIC CHARGES, MULTIPOLE MOMENTS AND VOLUMES QTAIM AND CORRELATION OF PHYSICOCHEMICAL PROPERTIES USE OF ATOMIC PROPERTIES IN QSAR USE OF BOND CRITICAL POINT PROPERTIES IN QSAR QTAIM AND MOLECULAR SIMILARITY USE OF QTAIM IN THEORETICAL SYNTHESIS OF MACROMOLECULES ASSUMED PERFECT TRANSFERABILITY IN THE SYNTHESIS OF A POLYPEPTIDE THE ASSEMBLY OF BUFFERED OPEN SYSTEMS IN A MACROSYNTHESIS THE LAPLACIAN OF THE DENSITY AND THE LEWIS MODEL THE LAPLACIAN AND ACID-BASE REACTIVITY MOLECULAR COMPLEMENTARITY THE USE OF THE MOLECULAR ELECTROSTATIC POTENTIAL IN MEDICIN CHEMISTRY AN EXAMPLE THAT FOCUSES ON VMIN – THE CARCINOGENICITY OF HALOGENATED OLEFINS AND THEIR EPOXIDES AN EXAMPLE FOCUSING ON THE GENERAL PATTERNS OF MOLECULAR ELECTROSTATIC POTENTIALS – TOXICITY OF DIBENZO-P-DIOXINS AND ANALOGS STATISTICAL CHARACTERIZATION OF THE MOLECULAR SURFACE ELECTROSTATIC POTENTIAL – THE GENERAL INTERACTION PROPERTIES FUNCTION (GIPF) SUMMARY ACKNOWLEDGMENT APPLICATIONS OF QUANTUM CHEMICAL METHODS IN DRUG DESIGN APPLICATION EXAMPLES FORCE FIELD PARAMETERS FROM AB INITIO CALCULATIONS EQUILIBRIUM GEOMETRY FOR A DOPAMINE-D3-RECEPTOR AGONIST SEARCHING FOR A BIOACTIVE CONFORMATION ATOMIC POINT CHARGES MOLECULAR ELECTROSTATIC POTENTIALS MOLECULAR ORBITAL CALCULATIONS OUTLOOK