Using a PDB File to Set Up a System for Simulation
Protein data bank
(PDB) files are almost universally employed in the biomolecular
simulation field. Unfortunately, using PDB files can be a painful
experience. Reasons for this include:
- Many PDB files do not adhere to the PDB standard.
- Much information that is necessary when setting up a system for simulation is absent from a PDB file.
- The experimentally-determined structures of proteins and
other biomolecules often have gaps or uncertainties. Thus, atoms may be
absent (e.g. hydrogens) or may be present several times (e.g. due to
the occurrence of multiple conformations for flexible parts of
Devising a fully automatic scheme for setting up a simulation
given a "well-behaved" PDB file and a "simple" system is relatively
straightforward. However, most cases are likely to require manual
intervention of some sort by the user.
A typical procedure that is followed when setting up a protein
system for simulation with pDynamo is listed below. The order of some of
the steps (particularly 4, 5 and 6) is variable and will depend on the
system being studied.
- Select a PDB file that is appropriate for the objectives of the simulation study.
- Step 1
- Read the PDB file and write out the PDB model that it contains to a file.
- Step 2
the PDB model file so that it conforms to the system that is to be
simulated. It is often more reliable to set up different parts of a
system separately, in which case the model file from Step 1 is
split up into several pieces.
- Step 3
- Create a system from the edited PDB model file and the original PDB file. The model file, along with the PDB component library
supplied with pDynamo, is used to generate the system's atoms and
bonds whereas the original PDB file provides atomic coordinates.
- Step 3a
- If there are errors in generating the system, it is most likely because not all the components, links and variants that appear in the PDB model have been defined. If not, these must be
added and Step 3 repeated.
- Step 4
- Generate an MM model for the system. At the moment this is only possible with the OPLS-AA force field.
- Step 4a
- Errors in Step 4
are common due to the absence of force field parameters that are needed
to describe various groups in the system. If this is the case, these
need to be added to the force field
definition and Step 4 repeated.
- Step 5
- Form the complete system by merging together its constituent parts if these were set up separately.
- Step 6
to see if the system has atoms whose coordinates are undefined or, in
other words, that were absent in the original PDB file. If so, these
must be constructed.
- Step 7
- Relax the structure of the vacuum system.
- Step 8
- Solvate the system using an appropriate solvent — normally water along with some counterions.
- Step 9
- Refine and equilibrate the structure of the solvated system in preparation for subsequent simulation.
The files employed in the different steps of this tutorial are available in the
tutorials/pdbFiles subdirectory of the pDynamo distribution.