Transcript Molecular Docking Using GOLD

Molecular Docking Using
GOLD
Tommi Suvitaival
Seppo Virtanen
S-114.2500
Basics for Biosystems of the Cell
Fall 2006
What is molecular docking?
• How a flexible ligand binds to a protein
• Ligand
– Small molecule compared to the protein
• Protein
– A macromolecule
– Might have an active site onto which the
ligand attaches
• Interactions
between the
cyclic urea
inhibitor and
HIV-1
protease
What is molecular docking? (2)
• Difficult to predict
• Parameters to be considered:
– Hydrogen bonds, lipophilic properties, van der
Waals interactions
– Possible metal ions
– Tensions of the ligand backbone
Conformation
GOLD
• ’Genetic Optimization for Ligand Docking’
• Input:
– Exact protein and ligand configurations in
order to get good results
– Demand for other programs specialized in
molecular visualization
• Genetic algorithm search method used to
search the different binding modes of the
ligands
• The binding mode has geometric and
chemical components
• Docked ligands ranked by fitness score
Fitness functions
• Several possible conformations depicted in one picture
Fitness functions
• For determining the rank between possible
geometries
• Two choices: GoldScore or ChemScore
– Different parameters used
• Calculations based on chemical and
physical theories
– Geometrical properties
– Bonding affinities
Genetic algorithm
• Initially a population of conformations is
generated
• Scoring algorithm evaluates the fitness of each
conformation
– conformation=chromosome
• Genetic operations occur
– Crossing-over
• Fit members of the population crossover and replace the
worst member of the population
– Migration
– Mutation
• Individual with
the best
properties is
the result
• Highest rank