Computational Drug Discovery and Design

systems require long computation times, often weeks to

months long. If a power failure occurs, the MD run is termi-

nated prematurely. In order to restart the calculation, we can

use the rst files saved with predefined frequencies. Suppose the

production run is interrupted. First, check the length of the

trajectory already calculated, by consulting the simulation time

at the end of the sys5.out file. Then, copy mdin5 file to a new

file called mdin6 and adjust the parameter nstlim so as to obtain

the initially desired length of the simulation after completing

this new stage. Then simply launch the script Run_pmemd_-

cuda again, specifying the total number of stages to be

6 and beginning simulations from stage #6. The program will

use the existing sys5.rst as input and continue the calculation of

the trajectory. If desired, the two trajectories, sys5.mdcrd and

sys6.mdcrd, can be combined by the ptraj or cpptraj utility

program.

3.4 Analysis
of the MD Trajectory

1. Monitor the time dependence of such variables as potential
   energy, density, and volume. The analysis will be performed
   on the equilibrated part of the trajectory, where these para-
   meters are stable. To do it, use a Perl script from the Amber
   website, available at the addresshttp://archive.ambermd.org/
   200507/att-0228/process_mdout.perl. It produces text files
   whose contents can be visualized by any plotting software. By
   looking at the graphs one can see from which frame the trajec-
   tory can be considered stable. This and all subsequent frames to
   the end of the trajectory will be used in clustering to find
   representative and distinct structures of the receptor.


2. The clustering procedure involves several steps. We will use the
   kclust routine from the MMTSB software package, available
   fromhttp://blue11.bch.msu.edu/mmtsb/Main_Page. In the
   first step we extract individual frames from the trajectory and
   put them as PDB files in a subdirectory. Run the following
   command: “ptraj sys.prmtop ptraj_PDB.in”, where the last
   argument is the file name containing the following lines:

trajin sys5.mdcrd 3001 10000 1

# remove solvent and ions

strip :291-999999

# remove trans & rot

center :1-290 mass origin

image origin center familiar

# best fit to the first frame

rms first mass :1-290@CA,C,N

# put all the pdb frames in a subdirectory

trajout PDB/frame.pdb pdb

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