- Copy the NAMD configuration script equil.conf to a new file
prod1.conf and update the input (equil) and output (prod1) file
names. - Run MD in NAMD on X processors by entering the following
command:
namd2 +pX prod1.conf >& prod1.log - Restart the MD simulation, continuing with NAMD runs for
files prod2, prod3, etc., until sufficient sampling of the system is
obtained. Given the performance of modern desktop worksta-
tions and supercomputers, publication quality MD simulations
of protein–ligand complexes commonly explore timescale of
hundreds of nanoseconds (seeNote 21).
5 Notes
- The model should describe the system at all-atom detail and
contains no missing regions. - The model must capture the chemical interaction between the
target protein and drug molecule. - The model should be free of structural clashes or close
contacts. - Any artifactualcispeptides in the model should be adjusted to
thetransorientation. - The reproduction of realistic solvent conditions is key to mean-
ingful simulation results. - Hydrogen coordinates and protonation states should be
assigned to reflect the desired pH of the model’s solvent
environment. - An explicit solvent representation should be employed to cap-
ture water-mediated hydrogen bonds between the target pro-
tein and drug. - Crystallographically resolved water molecules should be
retained in the model. - A distance of at least 15 A ̊ between the protein–drug complex
and the solvent box edges is recommended. - A cubic solvent box is most appropriate for long timescale
simulations. - Salt concentration of the solvent should mimic conditions of
the model’s realistic environment. - Careful placement of local salt ions around the model can
reduce equilibration time needed during the simulation phase
of the project.
Molecular Dynamics Simulations of Protein-Drug Complexes 267