BUSTER -forcefield option



The -forcefield refine option allows the use of a force field to represent a ligand. It uses the procedures developed for the Direct use of weighted Quantum Chemical Energy for ligands in BUSTER refinement. But instead of using a quantum chemical representation for the ligand a molecular mechanics force field is used. Initial work has concentrated on providing helpers for the MMFF94 force field (that is widely used and well regarded). Force fields offer a number of advantages compared to quantum methods:

  1. They are robust. Quantum methods have a tendency to fail for distorted or highly charged systems.
  2. They are computationally cheap.
  3. A well parameterized force field (like MMFF94) will give accurate results for molecules similar to those in its "training set". In these cases strain energy results comparable to computationally expensive accurate DFT calculations can be obtained (to be published).
  4. Force fields are extensively used in computational chemistry so results obtained from X-ray crystallography will be "computation ready". Furthermore, a high resolution X-ray complex including the ligand should validate the force field used (if a ligand is indicated to be highly strained then this would often indicate that the force field needs improvement.

The OpenEye implementation of MMFF94 includes extensions enabling the forcefield to represent compounds containing selenium (details) or boron (details). MMFF94 is used in the OpenEye AFITT automated ligand fitter.

How to set up OpenEye buster_helper_mmff


The RDKit helper

Using the -forcefield option

Specification of the ligands to represent with MMFF

refine -p model.pdb -m data.mtz -d 01 -l grade-LIG.cif -forcefield LIG > 01.log

Checking that the force field helper has correctly interpreted the ligand chemistry

refine -p model.pdb -m data.mtz -d rund -l grade-LIG.cif -forcefield LIG > run.log
    QM_HELPER_LOG: forcefield.pl invoking OpenEye Helper with /mnt/scratch_fs1/osmart/autobuster/Server/scripts/qm-mm-helpers/OpenEye.pl 0 1 AUTO
    QM_HELPER_LOG: gelly helper script to run OpenEye helpers for force field or QM energy/gradient calculation
    QM_HELPER_LOG: Please obtain helpers for OpenEye http://www.eyesopen.com/
    QM_HELPER_LOG: helper script location /mnt/scratch_fs1/osmart/autobuster/Server/scripts/qm-mm-helpers/OpenEye.pl
    QM_HELPER_LOG: picked up charge=0 multip=1 method=AUTO from command line
    QM_HELPER_LOG: Open Eye executable used:  /home/osmart/2013/09/OpenEyeHelper/openeye/bin//buster_helper_mmff
    QM_HELPER_LOG:            :jGf:
    QM_HELPER_LOG:         :jGDDDDf:
    QM_HELPER_LOG:     ,fDDLt:   :iLDDL;
    QM_HELPER_LOG:   ;fDLt:         :tfDG;
    QM_HELPER_LOG: ,jft:   ,ijfffji,   :iff
    QM_HELPER_LOG:     ;GDDGt:''':tDDDG,
    QM_HELPER_LOG:    .DDDG:       :GDDG.
    QM_HELPER_LOG:    ;DDDj         tDDDi
    QM_HELPER_LOG:    ,DDDf         fDDD,         Copyright (c) 2013
    QM_HELPER_LOG:     LDDDt.     .fDDDj          OpenEye Scientific Software, Inc.
    QM_HELPER_LOG:     .tDDDDfjtjfDDDGt
    QM_HELPER_LOG:       :ifGDDDDDGfi.            Version:
    QM_HELPER_LOG:           .:::.                Built:   20130710
    QM_HELPER_LOG:   ......................       OEChem version: 1.9.2 20130710
    QM_HELPER_LOG:   DDDDDDDDDDDDDDDDDDDDDD       Platform: Ubuntu-12.04-g++4.6-x64
    QM_HELPER_LOG: Input ISM: c1cc(ccc1C2C3CCCC3c4cc(ccc4O2)O)O
    QM energy for QMset    1 picked up as            316.47988
QM_HELPER_LOG: Input ISM: c1cc(ccc1C2C3CCCC3c4cc(ccc4O2)O)O
egrep ISM rund/01-BUSTER/Cycle-1/LIST.html | head -1 | sed -e 's/.*ISM..//' > check.smi
obabel check.smi -Ocheck.svg
convert check.svg check.png

Altering the weight used for -forcefield

Known limitations and issues

Currently the -forcefield option and helpers have the major limitation that ligands must be chemically complete with all hydrogen atoms. This limitation has consequences for handling both covalent and incomplete ligands.

Incomplete ligands

Ligands that are incomplete (have missing atoms) will not be handled properly at present. Any problem should be apparent by checking the SMILES string reported by the helper ISM line. It should be possible to fix this limitation in a future release.

Ligands that are covalently bound to the protein or other molecules

The current procedures will not properly handle covalently-bound ligands including proteins containing modified amino acids or nucleic acids with modified bases. Any problem should be apparent by checking the SMILES string reported by the helper ISM line. It should be possible to fix this limitation in a future release.

Ligands with alternate position atoms

The current procedure does not handle normal alternate positions in ligands. It is possible to treat alternates using a workaround, if you would like details contact buster-develop@globalphasing.com

It should be possible to fix this limitation in a future release.

grade S=O bond issue

Currently grade will incorrectly set the type for S=O bonds to "single". This will result in an incorrect force field setup, this will be shown by checking the SMILES string reported by the helper ISM line. For instance for the 1YU ligand from structure 4lxm the ISM SMILES produces a structure:


Back to Ligand QM/force field top index page

Page by Oliver Smart Nov 2013, modified June 2014 Any questions regarding our software or this wiki should be directed to buster-develop@globalphasing.com