protein ligand interactions 2

1. Protein – Ligand Interactions

2. Protein-ligand association
● Protein have the fundamental ability to selectively
bind to other molecules.
● Important for:
– Enzyme function.
– Receptor actions (membrane).
– Self-organization cellular structures and
– multicomponent protein complexes.
● Important to understand, both quantitatively and
qualitatively.

3. Protein-ligand binding
● Protein ligand binding
is a spontaneous
process.
● Similar forces as in
protein folding are at
work.
●
Function of proteins is
defined through its
interactions with other
molecules.
P + L PL⇔

4. Overview
● One or more possibly independent binding sites
● Cooperative effect:
– The binding of the first ligand may affect the binding of
the next ligand
– Positive, negative cooperative effect
● Multivalent interactions:
– Multiple possibly weak interactions between ligand and
protein can lead to a strong affinity

10. binding site comparison
protein ligand docking
MD simulation & MM/GBSA
Binding free energy calculation
structural proteome
off-target?
network construction
& mapping
drug target
Clinical Outcomes
1OHR
PHAR201 Lecture 12 2012PLoS Comp. Biol. 2011 7(4) e1002037