Dock Prep

Dock Prep performs several tasks to prepare structures for DOCK or for other calculations, such as:

• deleting water molecules
• repairing truncated sidechains
• adding hydrogens
• assigning partial charges
• writing files in Mol2 format

If extra molecules such as ligands or additional subunits are present but unwanted during docking, these should be deleted before Dock Prep is used. Dock Prep does not delete such molecules (other than water and certain ions, optionally) because they could be important for binding or for maintaining receptor structure. Conversely, the biologically relevant form of the receptor may contain more subunits than are present in the structure file. If important for downstream calculations, the relevant form should be generated before Dock Prep is run. For obtaining multimers, see: fetching PDB-biounit and PQS files, the command sym, Multiscale Models, 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 - convert modified residues to standard residues for which parameters are available:

• selenomethionine (MSE) to methionine (MET) - change MSE residues to MET by changing the selenium atom to a sulfur atom named SD and adjusting the CG-SD and SD-CE bond lengths to 1.81 and 1.78 Å, respectively
• bromo-UMP (5BU) to UMP (U) - change 5-bromouridine-5'-monophosphate (PDB chemical component 5BU) to RNA residue uridine-5'-monophosphate (U) by deleting the bromine atom
• methylselenyl-dUMP (UMS) to UMP (U) - change 2'-methylselenyl-2'-deoxyuridine-5'-phosphate (PDB chemical component UMS) to RNA residue uridine-5'-monophosphate (U) by replacing the methylselenyl moiety with an oxygen atom named O2' and adjusting the bond length to 1.430 Å
• methylselenyl-dCMP (CSL) to CMP (C) - change 2'-methylselenyl-2'-deoxycytidine-5'-phosphate (PDB chemical component CSL) to RNA residue cytidine-5'-monophosphate (C) by replacing the methylselenyl moiety with an oxygen atom named O2' and adjusting the bond length to 1.430 Å

• Incomplete side chains:
  
  
  • Replace using Dunbrack rotamer library
  • Replace using Richardson (common-atom) rotamer library
  • Replace using Richardson (mode) rotamer library
  • Mutate residues to ALA (if CB present) or GLY

    The rotamer library options replace each truncated sidechain with a complete sidechain of the same residue type, as if using the command swapaa with the specified rotamer library and preserve true (default settings of other options). If different settings are desired, use swapaa separately before using Dock Prep. The mutation option changes each residue with a truncated sidechain to glycine or alanine, the latter if a CB atom is present.

    Using one of these options to generate complete sidechains is recommended because in incomplete residues, the partial charges will not sum to integer values, and extra hydrogens (unrecognized in the charge addition step) will be added where the missing atoms would have been attached.

• Add hydrogens - call AddH for hydrogen addition. This tool aims to generate protonation states reasonable at physiological pH. For example, hydrogens are not added to the phosphodiester moieties of DNA and RNA. By default, aspartic acid and glutamic acid sidechains are assumed to be negatively charged, while arginine and lysine sidechains are assumed to be positively charged (although other states can be attained). Ambiguous groups are terminal phosphates (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.

  Potentially ambiguous or rare (shifted-pKa) protonation states, especially in binding sites and nonstandard residues, should be verified and corrected before charges are assigned. For example, extra hydrogens can be deleted, and atom types can be edited (before hydrogen addition) with setattr or Build Structure.

• 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 taken from Amber (details). 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.

Does not build missing segments. Structures may have missing residues or atoms where coordinates could not be determined because of disorder or flexibility. Dock Prep can fix truncated sidechains, but it will not build missing backbone segments.

• DOCK 6: combining techniques to model RNA-small molecule complexes. Lang PT, Brozell SR, Mukherjee S, Pettersen EF, Meng EC, Thomas V, Rizzo RC, Case DA, James TL, Kuntz ID. RNA. 2009 Jun;15(6):1219-30.
  
  
• Development and validation of a modular, extensible docking program: DOCK 5. Moustakas DT, Lang PT, Pegg S, Pettersen E, Kuntz ID, Brooijmans N, Rizzo RC. J Comput Aided Mol Des. 2006 Oct-Nov;20(10-11):601-19.