/
&gb
# for igb=5, use "set default PBradii mbondi2"
# in scripts producing prmtop files
# for igb=7, use "set default PBradii bondi" (not for nucleic
acids)
igb=5, saltcon=0.010
/
&pb
istrng=0.010,
indi=4,
/
&decomp
idecomp=1, print_res=’1-303’, csv_format=0,
dec_verbose=2,
/The &pb and &gb sections refer to the MM-PBSA and the
MM-GBSA methods, respectively (seeNote 12). As usual, adjust
the relevant variables as needed.- In order to perform pairwise energy decomposition, use the
above script with the following minor modifications: set ide-
comp to 3, and dec_verbose to 0 (otherwise the output will be
too voluminous). In both cases the output can be sorted to
focus on residues important for the intermolecular
interactions.
3.8 Concluding
Remarks
In conclusion, docking and MD are fully complementary. Docking
is fast and inexpensive, and MD allows taking into account a full
system flexibility giving more reliable and “realistic” interaction and
affinity information. MD is not an easy task and its protocols are
constantly improving with better algorithms and force fields, and in
parallel with better computer performance, allowing today to sim-
ulate a protein in the microsecond timescale and in complex
membrane-like environments. Docking with simultaneous MD
calculation would be an appropriate solution with all steps included
in one pass, but would currently take too long to simulate and
would face difficulties in the interpretation if the system got trapped
in local minima. Implementing MD protocols within a virtual
ligand screening process is necessary to increase the hit compounds
discovery success rate and enter a well-known “hit-to-lead” strategy
to obtain molecules with higher affinity and specificity against
medically relevant biological targets.
The choice of methods presented in this chapter has been
dictated by our own experience, but there are numerous
alternative approaches, which the readers are encouraged to explore
[63–70, 72].172 Gre ́gory Menchon et al.