Biology Reference
In-Depth Information
As an illustration of endpoint methods, we will review the molecular
mechanics-Poisson-Boltzmann surface area (MM-PBSA) models.
37,38
MM-PBSA
In MM-PBSA,
∆
G
bind
is written as the sum of the gas phase contribution,
∆
bind
; the energy difference due to translational and rotational degrees
of freedom,
H
gas
∆
H
trans/rot
; the desolvation free energy of the system upon
binding,
∆
G
desolv
; and an entropic contribution,
−
T
∆
S
37,38
:
gas
D
G
=
D
HH
+
D
+
D
G
-
T
D
S
.
bind
trans/rot
desolv
bind
bind
contains the van der Waals and electrostatic interaction
energies between the two partners in the complex, as well as the internal
energy variation (including bond, angle, and torsional angle energies)
between the complex and the isolated molecules,
The term
∆
H
gas
∆
H
intra
. In the classical
limit,
H
trans/rot
is equal to 3RT; this constant term is generally omitted
in MM-PBSA calculations.
∆
∆
G
desolv
is the difference between the solvation
free energy,
∆
G
solv
, of the complex and that of the isolated parts.
∆
G
solv
is
divided into the electrostatic,
∆
G
elec,solv
, and the nonpolar,
∆
G
np,solv
,
contributions:
D
G
=
D
G
+
D
G
.
solv
elec,solv
np,solv
G
elec,solv
is calculated by solving the Poisson or the
Poisson-Boltzmann equation,
39,40
depending on whether the salt concen-
tration is zero or nonzero. Recently, an approach related to MM-PBSA,
where
In MM-PBSA,
∆
G
elec,solv
is determined using a generalized Born (GB) model,
41
has
been introduced as molecular mechanics-generalized Born surface area
(MM-GBSA).
41,42
Despite its approximations, the GB model variant is
attractive since it is much faster than the PB model variant. Recent advances
of GB models
43,44
in reproducing the PB solvation energies of macromole-
cules as well as desolvation energies upon binding further support the use
of GB models in this context.
45
The term
∆
∆
G
np,solv
, which can be considered
