Free-energy calculations - Theoretical Biophysics Group

protein + ligand
0
∆ Aannihilation
protein + nothing
24 WADSÖ (1995)
∆ Abinding
∆ A =0
∆ Arestrain
25 FENN ET AL. (1989)
Free-energy perturbation calculations “Alchemical transformations”
protein ... ligand
1
∆ Aannihilation
protein ... nothing
26 KARLSSON, LARSSON (2004)
The binding free energy of two molecules, ∆Abinding,
defined as the free energy difference between these
molecules in the bound and the free, unbound states, can
be determined experimentally through the measurement
of binding constants using isothermal microcalorimetry, 24
electrospray ionization mass spectrometry, 25 or
BIAcore. 26
The computationally equivalent procedure corresponds
to calculating ∆Abinding directly, by means of an order parameter
that measures the separation between the ligand
and the binding center of the protein.
Definition of a relevant order parameter to describe
protein-ligand association may be difficult, in particular
when the ligand is buried deep in the binding pocket,
and access to the latter involves large conformational
changes in the protein.
Chris Chipot Free-energy calculations