Transcript Drug Docking

Drug Docking
Andrew Harris
Mark Clement
Kenneth Sundberg
Computer Science Department
Brigham Young University
Trypsinogen
Trypsin
Chymotrypsinogen
Chymotrypsin
Enterokinase
Duodenal Cell
Genetic Disease
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Some diseases caused by over-expression/underexpression of certain proteins or enzymes in a
given pathway
Down Syndrome – Trisomy 21, extra 21st
chromosome
Larger oral-pharyngeal anatomy
 Smaller jaw
 Learning disability
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Theoretically treatable with drugs
Drug Design Process
1.
2.
3.
Find Targets, Inhibitors, Compounds
Experiment Drug Candidates
Validate in vitro
Information
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ZINC, Human Genome Project now make this
sequence information available
Reduce time sifting through, predict side effects
PyMOL
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A molecular graphics visualization tool
Embedded Python interpreter
Open Source
Drug Docking Algorithm
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Searching
Superposition
 Rotation
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Scoring
Root Mean Square Deviation (RMSD)
 Bond Energies
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Searching
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Centroid Calculation, Geometric Translation
Matrix Multiplication Rotation
Scoring
Translation,
Rotation
Least RMSD score
Drug Docking Algorithm
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transpose centroids to the origin
foreach angular displacement in x
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foreach angular displacement in y
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foreach angular displacement in z
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Calculate RMSD
If this RMSD is less than current minimum, save it
Simple 3D Superposition and
Alignment
Modified Algorithm
Modified for Drug Docking
Biotin Docking to Streptavidin
Questions?