- Note that energy minimization is essential to resolve any high-
energy conformations in the structure that may introduce
instabilities during the simulation phase of the project (see
Note 17). Plotting the potential energy of the system versus
minimization step produces the plot given in Fig.10. Note that
energy decreases and reaches a plateau, indicating that 500 cycles
of minimization is sufficient for the system under study. - For more information on using NAMD, including documenta-
tion and tutorials, visit the NAMD software web page (http://
http://www.ks.uiuc.edu/Research/namd)..)
Step 14. Set up harmonic restraints for the system.- Return to VMD’s command line and generate a file to impose
positional (harmonic) restraints for the protein backbone and
drug molecule by entering the following commands:
set all [atomselect top "all"] ; # Select system
$all set beta 0 ; # Initialize beta column of PDB
set restraints [atomselect top "(protein and backbone) or resname TYL"] ; # Select restraint atoms
$restraints set beta 5 ; # Set force constant k=5 kcal/mol for restraint atoms
$all writepdb restraints.pdb ; # Write restraints PDB
Step 15. Run MD simulation of the system (heat with restraints).- Open a terminal and navigate to your working directory. Make
sure that the location of the NAMD executable is contained
within your $PATH variable. - Save the NAMD configuration script given below to your work-
ing directory as heat.conf.
Fig. 10Potential energy of the system decreases and reaches a plateau during minimization
Molecular Dynamics Simulations of Protein-Drug Complexes 263