This utility enables you to copy coordinates from a known structure or structures to a sequence whose structure is unknown. This process creates a homology model for the sequence that can be further refined using other modeling tools in Protein Design and other QUANTA applications, such as Conformational Search's Loop Modeling.
This utility generates the framework of a homology model by copying structure from homologues. The mainchain atom coordinates are copied directly from a known structure. Sidechain atom coordinates are copied as far as possible and any unresolved sidechain atom coordinates are built by regularization. You must decide the most appropriate homologues to copy coordinates from and the regions of the structure for which copying is valid (see the Protein tutorial).
The most efficient means to generate a model is to use the Auto Match tool in Align and Superpose to identify regions of sequence homology between the sequence of unknown structure and the known structure. Using a Match Window of say three or five residues (see under Match Options) will better identify homologous regions and exclude individual good matches. The Copy Matched Residues tool can then be used to copy coordinates for all the matched residues at once.
It is important to observe regions where two consecutive residues are modeled on different proteins. The two residues may not join well or may be too far away to form a bond. When this is observed, other tools should then be used to further refine the structure.
After remodeling the protein backbone by copying coordinates from a homologue, it is advisable to re-model the sidechains. The Auto Model tool on the Model Side Chains palette does this (see Chapter 9) and, to simplify the procedure, the Create Homology utility automatically writes a selection file, copy_side_sel.rsd, which lists the remodeled residues.
When the Create Homology Model utility is selected from the Protein Design palette the Choose an Unknown Structure dialog box opens with a scrolling list of all the active molecules. You need to select one of the molecules as the unknown structure. This sets that molecule as the structure being modelled. When the palette is displayed, all active molecules are listed under the COPY FROM tool, with the unknown structure grayed out. The unknown structure should be an MSF and not a sequence. MSFs can be created from sequences using the tool in the Protein Editor utility.
This option displays the Choose Unknown Structure dialog box with a scrolling list of all active molecules. The active molecule selected becomes the new unknown structure. This option allows you to change the selection of the unknown structure from the initial structure.
This tool activates the Pick Range palette. You can then pick the residue range over which the copying will be performed. This is done by picking the first and last residues of the range from either the sequence table or the molecule. Within this utility, the Active Range tool on the Utilities palette also has the same function as Select Copy Range.
This option displays the Copy Options dialog box, from which you select options for the visual display and mode of the copied coordinates.
This tool remains grayed out until a copy range has been selected on the unknown structure. Once this tool is active, selecting it copies the coordinates of the chosen known molecule to the unknown structure.
Copy the coordinates for all the residues currently matched. Matching residues are determined in the Align and Superpose utility by either an automated procedure to find homologous regions or by user selection. Matched residues are highlighted on the Sequence Viewer by a vertical yellow band. This highlighting is usually switched off outside the Align and Superpose module, but it is switched on again upon entering the Create Homology Model utility. If the Select Copy Range tool is active, then coordinates will only be copied for the matched residues within the selected range.
This tool saves the changes to the MSF of the unknown structure. The standard MSF saving dialogs are displayed.
This tool reads the last saved version of the MSF into QUANTA. Any changes not saved to the MSF are lost.
This tool exits the Create Homology Modeling palette and any changes remain active in memory. If the changes have not been saved, the standard save dialog boxes are displayed for saving the structural changes.