Biology Reference
In-Depth Information
of atoms (typically side chains). Like CAS, BFED also identifies the
nature of the energy change in terms of interaction and solvation ener-
gies, or entropic contributions. A detailed description of the BFED
process can be found elsewhere.
42,59
The MM-GBSA variant is attractive for BFED, not only because it
is much faster than MM-PBSA, but also because the pairwise nature of
the GB equation allows the decomposition of
G
elec,slov
into atomic con-
tributions in a straightforward manner.
42
It is, however, interesting to
note that the decomposition of a PB-calculated
∆
G
elec,slov
can also be
performed,
60
though it is more computationally demanding. Although
its results cannot be compared directly to an experimental AS, BFED
offers a faster alternative to CAS, since it only requires one binding free
energy calculation. Also, it allows studying the contributions from non-
mutable groups of atoms, such as backbone atoms. In addition, con-
trary to CAS, BFED is a nonperturbing approach that does not require
introducing a mutation into the system. A comparison between CAS
and BFED results can be found in Zoete and Michielin.
59
Obviously,
these methods cannot be expected to provide results exactly compara-
ble to values obtained from an experimental AS, since they both
neglect the effect of the mutations on the protein conformation.
However, fair agreements between the experimental and theoretical
results have been found in several studies and open the way to rational
protein engineering.
42,58,60,61
It has been found that the side chain contributions to
S
vib
play an
important role, and increase the quality of the correlation between exper-
imental and calculated energy changes.
42
A theoretically exact way to
calculate the contribution of a given group of atoms to
S
vib
is to zero their
mass and recalculate the normal modes and the corresponding total
entropy.
42
The difference between the wild-type system
S
vib
and that of
the system with some zeroed masses gives the contribution of the corre-
sponding atoms. This approach is very time-consuming, since it requires
an NMA for each group of atoms. Consequently, the entropic contribu-
tion is often neglected in such studies or calculated for the most impor-
tant residues only. However, a new vibrational entropy decomposition
scheme has been introduced recently to circumvent this problem: the linear
decomposition of the vibrational entropy (LDVE) approach,
59
∆
which
