Lecture 8

Question 0

Sampling

Answer 0

Exploration of confirmational and configurational space

Guides ligand placement

Question 1

Virtual screening

Answer 1

Alternative to HTS but usually preformed with HTS because validation is always required, there are solvent errors, and protein structure errors

Question 2

Scoring

Answer 2

Evaluation of strength of receptor-ligand interaction

H bonds are influenced by distance, angle of approach and charge

Question 3

Quantitative structure activity relationship

Answer 3

Basis of quantitative drug

Biological properties are a function of the physiochemical parameters

Question 4

Lipophilicity

Answer 4

Drug to target

Question 5

Electronic effects

Answer 5

What happens at target

Question 6

Sterics

Answer 6

Can it fit in target

Question 7

3-D – QSAR

Answer 7

Assay set of molecules➡️align molecules according to orientation rules➡️calculate a set of spatially dependent parameters➡️ derive function relating each molecules spatial parameters to their biological properties➡️ establish consistency and predictability of function

Question 8

Comparative molecular filled analysis CoMFA

Answer 8

Molecular-receptor interactions are represented by steric and electrostatic fields exerted by each molecule

IDs where lower and higher steric or electrostatic interactions increase binding

Question 9

CADD advantages

Answer 9

Every amino acid position know.
Easy manipulation of angles and Zoom. 
Physiochemical properties viewed and overlaid to determine possible interactions. 
Distance for H bonding. 
Determination of fit and interactions