qmd


SYNOPSIS

qmd  [prm=<folder containing TINKER parameter files>]  \
    [keep_initial={YES | NO; defaults to NO}]  \
    [minimizer={OPTIMIZE | MINIMIZE; defaults to OPTIMIZE}]  \
    [min_maxiter=<maximum number of iterations carried out by the minimizer>; defaults to 1000]  \
    [min_grad=<RMS gradient criterion to be satisfied by the minimizer>; defaults to 0.001]  \
    [rmsd=<heavy atom RMSD below which two conformers are considered identical>; defaults to 0.2]  \
    [range=<maximum energy delta from the global minimum beyond which conformers are discarded>; defaults to 3.0]  \
    [temperature=<temperature in K at which molecular dynamics are carried out>; defaults to 1000]  \
    [runs=<number of molecular dynamics runs carried out>; defaults to 200]  \
    [window=<length in ps of each molecular dynamics run>; defaults to 10]  \
    [time_step=<length in fs of the molecular dynamics integration time step>; defaults to 1.0]  \
    [diel_const=<dielectric constant value>; defaults to 1.0]  \
    [gbsa={YES | NO}; defaults to NO]  \
    [qmd_dir=<directory where SDF databases of conformers are stored>]  \
    [remove_qmd_folder={YES | NO}; defaults to NO]


DESCRIPTION

The qmd keyword is used to carry out quenched molecular dynamics (QMD) conformational searches. The quenched molecular dynamics protocol we implemented in Open3DALIGN is outlined below:
  1. minimize the starting geometry using the MMFF94s force-field as implemented in TINKER; the TINKER minimizer can be chosen through the minimizer parameter, which defaults to OPTIMIZE
  2. run a short molecular dynamics run using the MMFF94 force-field as implemented in TINKER (e.g., 10 ps, controlled by the window parameter) at high temperature (e.g., 1000 K, controlled by the temperature parameter). The integration time step can be modified through the time_step parameter (default: 0.1 fs)
  3. minimize the resulting geometry using the MMFF94s force-field as implemented in TINKER until the RMS gradient drops below a threshold value (e.g., 0.001 kcal mol-1 Å-1, controlled by the min_grad parameter) or, alternatively, the maximum number of allowed minimization iterations is reached (e.g., 1000, controlled by the min_maxiter parameter). MMFF94 and MMFF94s parameters are read from the files mmff.prm and mmffs.prm respectively. Open3DALIGN looks for these files in the folder specified by the prm_dir parameter; the latter defaults to the parameters folder which is expected to lie in the share/tinker folder, one directory level upper with respect to the bin folder where the Open3DALIGN executable is (that is, bin/../share/tinker, as is the case with the pre-built distributions).
  4. compare the obtained conformer with those already stored during previous QMD cycles: if the RMS deviation is larger than a threshold value (e.g., 0.2 Å, controlled by the rmsd parameter), then store it otherwise discard it. This comparison takes into account simmetry and has been realized by implemementing the combined SDM/RMS algorithm described by Michel Petitjean [1].
  5. Go back to point 1 until the maximum number of allowed QMD cycles is reached (e.g., 200, controlled by the runs parameter).

The simulation can be carried out in the absence of solvent, setting the dielectric constant of the medium through the diel_const parameter (default: 1.0), or in implicit solvent according to the GBSA model as implemented in TINKER.
At the end of the QMD conformational search, the lowest energy conformer is considered the global minimum and all conformers having an energy delta from the global minimum larger than a certain threshold value (e.g., 3.0 kcal mol-1, controlled by the range parameter) are discarded. If the keep_initial parameter is set to YES, then the initial geometry will be included in the QMD database, regardless of its energy delta with respect to tjhe global minimum. The remaining conformers are stored in a SDF database inside the folder specified through the qmd_dir parameter; the latter defaults to a folder named O3A.####.qmd_dir.######, where the #'s stand for random alphanumeric characters, located in the same folder from which the dataset SDF file was imported. If the remove_qmd_folder is set to YES (the default is NO), the temporary folder containing TINKER intermediate files is removed. Keeping the folder allows to postprocess the QMD trajectory at a later stage, for instance modifying the energy threshold/RMSD similarity criteria, without need to repeat the whole conformational search; instead, it will be sufficient to delete the ####.sdf conformational databases and specify as qmd_dir the same folder as in the previous run.

In summary, the same QMD procedure is repeated for the n compounds belonging to the currently loaded dataset, and conformers are saved into n SDF databases in the directory defined by qmd_dir. Therefore, after importing a SDF database of n compounds through the import type=SDF keyword, the qmd keyword yields a directory with n SDF databases containing the most stable conformer in a span from the global minimum selected through the range parameter.

By default, the qmd module operates in parallel fashion on multiprocessor machines, using all the CPUs available in the system; if one wishes to run the computation on a lower number of CPUs, this may be specified before calling qmd with the env n_cpus keyword.

Since QMD searches can be time-consuming, especially when large datasets and high numbers of runs are used, unfinished runs which have been stopped by CTRL-C, logout, shutdown, etc. can be very easily restarted using the same keywords as in the interrupted run, simply specifying the qmd_dir where SDF conformational databases have been previously written; Open3DALIGN will be able to automatically restart the QMD search from the point where it had been interrupted.

REFERENCES

  1. Petitjean, M. Computers Chem. 1998, 22, 463-465.   DOI

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May 31. 2015 20:39:55

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