Drug DockingDrug Docking

Computer Science Computer Science DepartmentDepartment

Brigham Young UniversityBrigham Young University

Andrew HarrisAndrew Harris

Mark ClementMark Clement

Kenneth SundbergKenneth Sundberg

Trypsinogen

Trypsin

Chymotrypsinogen

Chymotrypsin

Duodenal Cell

Enterokinase

Genetic DiseaseGenetic Disease

Some diseases caused by over-Some diseases caused by over-expression/under-expression of expression/under-expression of certain proteins or enzymes in a given certain 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

Drug Design ProcessDrug Design Process

1.1. Find Targets, Inhibitors, Find Targets, Inhibitors, CompoundsCompounds

2.2. Experiment Drug CandidatesExperiment Drug Candidates

3.3. Validate Validate in vitroin vitro

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

PyMOLPyMOL

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

Drug Docking AlgorithmDrug Docking Algorithm

SearchingSearching SuperpositionSuperposition RotationRotation

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

SearchingSearching

Centroid Calculation, Geometric Centroid Calculation, Geometric TranslationTranslation

Matrix Multiplication RotationMatrix Multiplication Rotation

ScoringScoring

Translation,Rotation

Least RMSD score

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

Simple 3D Superposition Simple 3D Superposition and Alignmentand Alignment

Modified AlgorithmModified Algorithm

Modified for Drug Modified for Drug DockingDocking

Biotin Docking to Biotin Docking to StreptavidinStreptavidin

Questions?Questions?