Dock Prep

Dock Prep can perform several tasks to prepare structures as input to the DOCK suite of programs (or for other types of calculations), including:

• removal of solvent
• deletion of alternate locations of atoms
• hydrogen addition
• partial charge assignment
• writing files in Mol2 format

If there are extra molecules other than solvent that should not be present during docking, these should be deleted before Dock Prep is run. Dock Prep does not delete extra chains or other molecules besides solvent, because depending on the specific situation, they might be important for binding or maintaining receptor structure. Similarly, binding might require the presence of more chains than are included in the structure file; the relevant form should be generated before Dock Prep is run (see also Unit Cell).

There are several ways to start Dock Prep, a tool in the Structure Editing category (including using it via Minimize Structure).

Under Molecules to prep, the structure(s) of interest should be chosen from the list of open molecule models. Individual models or blocks of models can be chosen with the left mouse button. Ctrl-click toggles the status of an individual model. To choose a block of models without dragging, click on the first (or last) and then Shift-click on the last (or first) in the desired block.

Several operations can be performed on the chosen structures:

• Delete solvent - delete any solvent molecules (usually waters). This is generally done to prepare a receptor structure for docking. If any solvent molecules are thought to be important for ligand binding, however, one should manually delete the other solvent residues beforehand and deactivate this option in Dock Prep.
  
  
• Delete non-complexed ions - delete any ions that are not participating in covalent or coordination bonds (by default, the latter are shown as dashed lines). This bonded-or-not distinction is based solely on input bond specifications such as CONECT and LINK records in PDB files; it is not inferred from the chemistry of the system.
  
  
• If alternate locations, keep only highest occupancy - for atoms with alternate locations, retain only the highest-occupancy set (if a tie, the set with a lower B-factor where the alternate locations branch from the common structure)
  
  
• Change selenomethionine (MSE) to methionine (MET) - change the name of MSE residues to MET, and in each of those residues, change the selenium atom to a sulfur atom of type S3 named SD. The CG-SD and SD-CE bond lengths are adjusted to 1.81 and 1.78 Å, respectively. This residue conversion is useful because charges and other parameters are available for MET but not MSE. Furthermore, the natural protein probably contains methionine rather than selenomethionine (proteins are generated with selenomethionine because Se atoms are useful in X-ray structure determination).
  
  
• Mutate residues with incomplete side chains to ALA (if CB present) or GLY - change each residue with a truncated side chain to alanine if the residue has a CB atom, glycine if it does not. Otherwise, the partial charges in such residues will not sum to integer values because of the missing atoms, and extra hydrogens (unrecognized in the charge addition step) will be added where the missing atoms would have been attached.

  An alternative approach is to repair truncated sidechains with Rotamers beforehand.

• Add hydrogens - call AddH for hydrogen addition. Protonation states are intended to be reasonable at physiological pH. For example, phosphodiester moieties and carboxylates including aspartate and glutamate sidechains are assumed to be negatively charged; arginine and lysine sidechains are assumed to be positively charged. Moieties treated as ambiguous are terminal phosphate groups (the third ionization) and imidazoles such as histidine sidechains. Histidine protonation states can be user-specified or guessed by the method. Whether a terminal phosphate is triply ionized is guessed using bond lengths. Additional rules are used to identify and handle chain termini.

  The resulting protonation states of such groups and of those with possibly perturbed pKa values (for example, in active sites or coordinating metal ions) should be checked manually and corrected as needed. Correction may consist of deleting unwanted hydrogens (for example, with Atoms/Bonds... delete in the Actions menu) or adding hydrogens that were not added automatically (for example, with Build Structure). Charge assignment should be repeated after any manual correction of protonation states.

• Add charges - call Add Charge to assign partial charges to atoms. Partial charges are assigned as an atom attribute named charge and will be included in Mol2 output.

  Charges for standard residues (water, standard amino acids, standard nucleic acids, and a few common variants and capping groups) are looked up using assignment files based on the Amber parameter files all*94.lib. If any atoms in standard residues are not recognized, a warning will appear and information on the atoms will be sent to the Reply Log. Cases of unrecognized atoms in standard residues and/or incorrect net charges should be examined and resolved.

  Charges for nonstandard residues, if any, are calculated using Amber's Antechamber module (included with Chimera; publications involving its use should cite the reference). It is necessary to specify the formal charge of each nonstandard residue and which charge calculation method should be used.

• Write Mol2 file - open a dialog for saving Mol2 files; options include saving coordinates relative to the untransformed coordinates of a particular model, generating an @SET section containing the selected atoms (as used to specify the rigid portion of a ligand in DOCK), and saving multiple models in a single file or multiple files

Tasks are performed in the order listed on the Dock Prep dialog. If any individual step is canceled, subsequent steps will not be performed; for example, if charge assignment is canceled, a Mol2 file will not be written. To skip a particular step, uncheck its option before initiating the Dock Prep calculation.

A related tool is ViewDock, which facilitates interactive screening of DOCK output.

Does not build missing residues or truncated sidechains. Structures may have missing residues or atoms where coordinates could not be determined, often due to disorder or flexibility. Dock Prep does not build in any missing residues or truncated sidechains. C-terminal OXT atoms are the only heavy (nonhydrogen) atoms that will be added when missing from a structure. Residues with truncated sidechains can be mutated to alanine or glycine depending on whether CB atoms are present.