Calculating the Secrets of Life

Eric S. Lander and Michael S. Waterman, Editors; Committee on the Mathematical Sciences in Genome and Protein Structure Research, National Research Council

• Front MatterChapter 1 The Secrets of Life: A Mathematician's Introduction to Molecular Biology BIOCHEMISTRYCLASSICAL GENETICSMOLECULAR BIOLOGYTHE RECOMBINANT DNA REVOLUTIONMOLECULAR GENETICS IN THE 1990STHE HUMAN GENOME PROJECTCOMING ATTRACTIONSREFERENCESChapter 2 Mapping Heredity: Using Probabilistic Models and Algorithms to Map Genes and Genomes The Concept of Genetic MapsChallenges of Genetic Mapping: Human Families and Complex TraitsMAXIMUM LIKELIHOOD ESTIMATIONEfficient AlgorithmsExcursion: Susceptibility to Colon Cancer in Mice and the Large Deviation Theory of Diffusion ProcessesAssembling Physical Maps by "Fingerprinting" Random ClonesExcursion: Designing a Strategy to Map the Human GenomeCONCLUSIONREFERENCESChapter 3 Seeing Conserved Signals: Using Algorithms to Detect Similarities between Biosequences FINDING GLOBAL SIMILARITIESVisualizing Alignments: Edit GraphsThe Basic Dynamic Programming AlgorithmFINDING LOCAL SIMILARITIESVariations in Gap Cost PenaltiesThe Duality Between Similarity and Difference MeasuresAligning More Than Two Sequences at a TimeK-Best AlignmentsApproximate Pattern MatchingParallel ComputingCOMPARING ONE SEQUENCE AGAINST A DATABASEHeuristic AlgorithmsSublinear Similarity SearchesOPEN PROBLEMSREFERENCESChapter 4 Hearing Distant Echoes: Using Extremal Statistics to Probe Evolutionary Origins Sequence AlignmentAlignment GivenAlignment UnknownAlignment GivenAlignment UnknownAPPLICATION TO RNA EVOLUTIONTWO BEHAVIORS SUFFICERNA EVOLUTION REVISITEDREFERENCESChapter 5 Calibrating the Clock: Using Stochastic Processes to Measure the Rate of Evolution OVERVIEWTHE COALESCENT AND MUTATIONThe Ewens Sampling FormulaTop-downBottom-upThe Infinitely-Many-Sites ModelK-Allele ModelsThe Finitely-Many-Sites ModelsApproximations for the Ewens Sampling FormulaCombinatorial AssembliesOther Combinatorial StructuresThe Large ComponentsWHERE TO NEXT?Likelihood MethodsDiscussionGeneral-Purpose ReferencesDetailed ReferencesChapter 6 Winding the Double Helix: Using Geometry, Topology, and Mechanics of DNA DNA GEOMETRY AND TOPOLOGY: LINKING, TWISTING, AND WRITHINGAPPLICATIONS TO DNA TOPOISOMERASE REACTIONSDNA ON PROTEIN COMPLEXESTHE SURFACE LINKING NUMBERTHE WINDING NUMBER AND HELICAL REPEATRELATIONSHIP BETWEEN LINKING, SURFACE LINKING, AND WINDINGAPPLICATION TO THE STUDY OF THE MINICHROMOSOMEREFERENCESChapter 7 Unwinding the Double Helix: Using Differential Mechanics to Probe Conformational Changes...DNA SUPERHELICITY - MATHEMATICS AND BIOLOGYSTATEMENT OF THE PROBLEMTHE ENERGETICS OF A STATEANALYSIS OF SUPERHELICAL EQUILIBRIAEvaluation of Free-Energy ParametersAccuracy of the Calculated ResultsAPPLYING THE METHOD TO STUDY INTERESTING GENESDISCUSSION AND OPEN PROBLEMSREFERENCESChapter 8 Lifting the Curtain: Using Topology to Probe the Hidden Action of Enzymes THE TOPOLOGY OF DNASITE-SPECIFIC RECOMBINATIONTOPOLOGICAL TOOLS FOR DNA ANALYSISTHE TANGLE MODEL FOR SITE-SPECIFIC RECOMBINATIONTHE TOPOLOGY OF TN3 RESOLVASESOME UNSOLVED PROBLEMSApplication of Geometry and Topology to BiologyREFERENCESChapter 9 Folding the Sheets: Using Computational Methods to Predict the Structure of Proteins A PRIMER ON PROTEIN STRUCTUREBASIC INSIGHTS ABOUT PROTEIN STRUCTURETHREADING METHODSPREDICTING HIV PROTEASE STRUCTURE:AN EXCURSIONHIERARCHICAL APPROACHESPREDICTING MYOGLOBIN STRUCTURE:AN EXCURSIONACKNOWLEDGMENTSREFERENCESAppendix - Chapter AuthorsIndex