Biomedical Engineering Reference
In-Depth Information
CHAPTER 10
Non-Canonical Ligand-Binding
Events as Detected by NMR
ERIK R. P. ZUIDERWEG
The University of Michigan Medical School, 1150 West Medical Center Drive,
Ann Arbor, MI 48109, USA
E-mail: zuiderwe@umich.edu
10.1
A Brief Refresher on NMR-Focussed Ligand
Binding
10.1.1 Ligand Binding Thermodynamics and Kinetics
Consider the simple equilibrium
k
f
PzL
/
?
PL
ð
10
:
1
Þ
k
b
Here, P is a protein (receptor) and L is the ligand. The rate k
b
is the off-rate,
which reflects the efficiency of thermal fluctuations to shake loose the ligand,
and is a real measure of the stability of the interaction. k
f
is the on-rate, which
describes the efficiency of the collisions. The on-rate reflects the probability of
a productive collision, and is hence related to the basic collision dynamics and
the entropy gain/loss due to restriction in configuration for both partners when
the interaction is established. When every collision is productive, the on-rate is
set by diffusion. This diffusion-controlled on-rate is only weakly dependent on
molecular size, but is dependent on molecular charge, shape and target area for
