Drug Docking

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Drug Docking Drug Docking Computer Science Computer Science Department Department Brigham Young University Brigham Young University Andrew Harris Andrew Harris Mark Clement Mark Clement Kenneth Sundberg Kenneth Sundberg

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Drug Docking. Andrew Harris Mark Clement Kenneth Sundberg. Computer Science Department Brigham Young University. Trypsinogen. Trypsin. Chymotrypsinogen. Chymotrypsin. Enterokinase. Duodenal Cell. Genetic Disease. - PowerPoint PPT Presentation

Transcript of Drug Docking

Page 1: Drug Docking

Drug DockingDrug Docking

Computer Science Computer Science DepartmentDepartment

Brigham Young UniversityBrigham Young University

Andrew HarrisAndrew HarrisMark ClementMark Clement

Kenneth SundbergKenneth Sundberg

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Trypsinogen

Trypsin

Chymotrypsinogen

Chymotrypsin

Duodenal Cell

Enterokinase

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Genetic DiseaseGenetic Disease Some diseases caused by over-Some diseases caused by over-

expression/under-expression of certain expression/under-expression of certain proteins or enzymes in a given proteins or enzymes in a given pathwaypathway

Down Syndrome – Trisomy 21, extra Down Syndrome – Trisomy 21, extra 2121stst chromosome chromosome Larger oral-pharyngeal anatomyLarger oral-pharyngeal anatomy Smaller jawSmaller jaw Learning disabilityLearning disability

Theoretically treatable with drugsTheoretically treatable with drugs

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Drug Design ProcessDrug Design Process1.1. Find Targets, Inhibitors, Find Targets, Inhibitors,

CompoundsCompounds2.2. Experiment Drug CandidatesExperiment Drug Candidates3.3. Validate Validate in vitroin vitro

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InformationInformation ZINC, Human Genome Project now ZINC, Human Genome Project now

make this sequence information make this sequence information availableavailable

Reduce time sifting through, predict Reduce time sifting through, predict side effectsside effects

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PyMOLPyMOL A molecular graphics visualization toolA molecular graphics visualization tool Embedded Python interpreterEmbedded Python interpreter Open SourceOpen Source

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Drug Docking AlgorithmDrug Docking Algorithm SearchingSearching

SuperpositionSuperposition RotationRotation

ScoringScoring Root Mean Square Deviation (RMSD)Root Mean Square Deviation (RMSD) Bond EnergiesBond Energies

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SearchingSearching Centroid Calculation, Geometric Centroid Calculation, Geometric

TranslationTranslation Matrix Multiplication RotationMatrix Multiplication Rotation

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ScoringScoring

Translation,Rotation

Least RMSD score

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Drug Docking AlgorithmDrug Docking Algorithm

transpose centroids to the origintranspose centroids to the origin foreach angular displacement in xforeach angular displacement in x

foreach angular displacement in yforeach angular displacement in y foreach angular displacement in zforeach angular displacement in z

Calculate RMSDCalculate RMSD If this RMSD is less than current minimum, save itIf this RMSD is less than current minimum, save it

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Simple 3D Superposition Simple 3D Superposition and Alignmentand Alignment

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Modified AlgorithmModified Algorithm

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Modified for Drug Modified for Drug DockingDocking

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Biotin Docking to Biotin Docking to StreptavidinStreptavidin

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Questions?Questions?