Bioinformatics 19: Structural 4

Question 1

What interactions are present during ligand docking? How can they be quantified?

Answer 1

Non-covalent interactions

• Hydrogen bonds (weak electrostatic)
• charge interactions, salt bridges (strong electrostatic)
• van-der-Waals (hydrophobic)
• aromatic interactions, pi-stacking (hydrophobic)
• shape complementarity

Can be quantified with the help of force fields

Question 2

What is ligand docking? (in bioinformatics)

Answer 2

Bioinformatics method used in drug discovery

-> predict binding mode + affinity of ligand in binding site of receptor

Question 3

Main uses of ligand docking?

Answer 3

High throughput docking (virtual screening)

Predicting binding modes

Predicting binding energies

Question 4

Purpose of High throughput docking virtual screening) ?

Answer 4

Find new lead compounds in huge databases, generate enriched lists to prioritise synthesis and other testing

• often together with experimental high throughout screening

Question 5

Purpose of predicting binding modes?

Answer 5

Structure based drug design, often as part of bigger experimental efforts - or when X-ray not possible

Guide medical chemists for synthesis of new compounds

allows in silico ‘testing’ of virtual compounds

Question 6

Purpose of predicting binding energies?

Answer 6

Useful for finding trends, but scoring functions often not accurate enough

Question 7

What is CAFA? Purpose?

Answer 7

Critical Assessment of Function Annotation
-> similar to CASP, assessment of function prediction

Attempts so solve problem: many known protein sequences, but function is unknown