This utility contains tools for modeling the protein side chain conformations. It is assumed that the protein main chain has been determined using the Model Backbone utility.
When side chains are altered by either the Mutate tools in the Protein Editor or the Copy tools in Create Homology Model the conformation of the side chain is retained as much as possible from the original structure and generally in homology modeling it is best to retain as much as possible from the homolog but for residues for which there is no homology evidence on which to base the side chain conformation this utility provides rotamer library and energetics tools to best fit the side chain.
Sidechains should not overlap with neighboring residues so this utility incudes tools to indicate close contacts and to perform energy minimization which will attempt to eliminate close contacts. But minimization will only find local minima and the rotamer and spin tools should be used to search through conformational space. Side chain modeling can be performed in a manual mode, analyzing each side chain individually. Alternatively, an automatic mode will allow you to select multiple residues which will all be fitted using rotamer libraries and minimization.
There is a tool to perform modeling of any number of selected side chains using one selected rotamer library and optionally using regularization. For each side chain, all rotamer conformations will be tested and the one with least close contacts selected. The energy minimization will then find the best local conformation. The minimization does take account of van der Waals interactions.
This tool can be used after the protein backbone has been significantly remodeled; for example in the Create Homology Model utility, in Model Backbone, Fragment Database and in the Protein Editor. In all of these utilities, when a section of backbone is remodeled the affected residues are listed to a QUANTA selection file and this file can be used to select the residues for automatic side chain modelling. The selection files generated automatically by the Create Homology Model, Fragment Database and Protein Editor utilities are called copy_side_sel.rsd, fragment_side_sel.rsd and edit_side_sel.rsd, respectively. A new file is created on entering the utility and any existing file is overwritten so if you wish to save one of these selection files you must move it to a new file name.
The selection of residues for automatic side chain modeling is done through a standard selection palette which has the option to read a selection from a file, Read Selection-Commands on the Selection Utilities palette.
Close contacts can be displayed using the Display Contacts tool. The criteria for determining close contacts is basically the same as used in the Bumps tool in fragment searching in the Model Backbone utility. All atoms closer than the specified bump cut-off distance are flagged. The default is set at 3.0 Å. If the structure includes hydrogens, then the bump cutoff is further reduced.
There are several analyses of the protein database that classify commonly occurring conformations for each residue type. These classifications are called rotamers. The Protein Design application uses three of these analyses in modeling sidechains. The three rotamer libraries are Ponder and Richards; Sutcliffe; and Dunbrack and Karplus. These three rotamer libraries are based on different analyses of the side chain dependence on the backbone conformation. See the Protein Health chapter for more information.
The Ponders and Richards analysis ignores the main chain conformation of a residue. The Sutcliffe analysis specifies whether each rotamer is for a helix, strand, or any main chain conformation.
Dunbrack and Karplus base their analysis on the side chain conformation as a function of the main chain f and y angle. A statistical analysis for each residue type groups together residues with f/y values within a given range of positions on a two-dimensional grid. For each group of residues of similar main chain conformation, the number of occurrences of each possible side chain rotamer is counted.
The possible sidechain rotamer conformations for chi c1 and c2 dihedrals are defined as:
gauche + torsion range centered on + 60×
gauche - torsion range centered on - 60°
trans torsion range centered on 180×
The subsequent dihedrals for longer sidechains are ignored.
When the current residue is modeled, the library is searched for the data for the f/y grid point closest to the f/y of the current residue. All rotamers with one or more occurrences for that grid point are considered. The c values of the current residue are set to the ideal values for each rotamer.
The Spin tool scans the conformation space for the side chain by incrementing the dihedral by some fixed amount. The conformation is then tested for close contacts with neighboring residues. When a conformation without close contacts is found, it is displayed. For the longer side chains with two or more variable torsions, the search works by rapidly rotating the most remote bond from the main chain.
The default spin increment is 30×. When the initial conformation has no close contacts, the spin algorithm assumes a minimum energy well and ignores all acceptable conformations until a conformation with close contacts is found. After the spin search has covered the whole conformational space, the side chain is returned to its initial conformation. If none of the conformations are without close contacts, the spin search is repeated with the bump cutoff distance decreased, allowing marginally closer contacts.
There are two modes for using this utility - the automated mode allows you to select all the residues of interest and then goes through them all automatically finding the rotamer which fits with fewest bad contacts and then, optionally, minimizing the residue.
In the manual mode, the residue whose sidechain is currently being modeled is designated the current residue There are tools which can either pick the current residue or step forward or backward through the sequence.
There are a series of tools for modeling the current residue. Only one tool can be active at a time, while the remaining tools are grayed out. When more than one conformation is possible, as with the rotamer libraries, the Spin and Copy Homologous tools, then the Next Conformation tool can be used to step through the possible models.
At the bottom left of the display, the initial and current torsions for the current residue side chain are displayed. At the bottom of the display, a text line reports the identity of the current residue and which modeling method was used to generate the current model. The text line also gives a conformation number for those methods, such as rotamer libraries, and spin which generate multiple models. For the rotamer libraries, the percentage of the side chains observed in this conformation is reported, and for the Karplus rotamers, the main chain conformation is also reported.
As you step through the display of multiple conformations for the rotamer libraries or for spinning, the number of close contacts and possible hydrogen bonds is reported in the textport.
The Residue Selection palette is presented so you can select any number of residues. You then have the option of which rotamer library to use and whether or not to minimize. The procedure runs through all the selected residues, finding the rotamer with the fewest bad contacts and then optionally refining that conformation.
This tool allows you to pick the next residue, either in the molecule or in the sequence viewer, that will become the current residue.
This tool selects the next residue in the sequence that becomes the current residue.
This tool selects the previous residue in the sequence that becomes the current residue.
This tool toggles on the display of all atoms.
When modeling side chains, it is often useful to limit the display to a sphere around the current residue. If multiple molecules are displayed, then for each non-active molecule the display sphere is taken around the residue equivalent to the current residue. It is helpful to have any homologous proteins correctly superposed over the active molecule. By default, the display sphere is 6 angstrom, but this can be altered with the Options tool.
This tool displays only the current residue and any equivalent residues in non-active molecules.
This tool displays close contacts between the current residue and neighboring residues in the active molecule. As the side chain conformation is changed, the contacts are updated.
This tool activates the Selection palettes that allow you to select residues. If any atom in these selected residues has undefined coordinates, then templates for idealized side chain geometry found in $HYD_LIB/protein_structure.gsd are used to generate the atom coordinates.
This tool restores the current residue to its initial conformation. If several residues have been modeled, they all are restored to their initial conformation by the ReRead MSF tool. It is advisable to save the modeling results frequently using the Save to MSF tool.
This tool increments the side chain torsions by 30° or by the value set by Options tool, until it finds a conformation with no close contacts or a minimum number of close contacts. The Next tool steps to the next conformation with no contacts.
This tool activates a pseudo-dial set for rotating bonds.
This tool copies the side chain conformation from the equivalent residue- the aligned residue in the sequence viewer- to the current residue. If there is more than one equivalent residues, the Next Conformation tool can be used to step through displaying each of them. The actual number of torsions copied for all possible residue type pairs is defined in the Equivalent Torsion Lookup Table in the file $HYD_LIB/protein_param.dat. Any remaining torsions in the current residue side chain retain their previous value.
This tool sets the current residue to the optimal rotamer of the Ponders and Richards rotamer library. If there is more than one rotamer, the Next Conformation tool can be used to step through them.
This tool sets the current residue to the optimal rotamer of the Sutcliffe rotamer library. If there is more than one rotamer, the Next Conformation tool can be used to step through them.
This tool sets the current residue to the optimal rotamer of the Dunbrack and Karplus rotamer library. If there is more than one rotamer, the Next Conformation tool can be used to step through them.
This tool provides a dialog box to changes the required torsions.
Energy minimization is performed for the individual residue.
This tool displays the Side Chain Modeling Options dialog box from which you can change default variables.
The options are described in the following section.
This specifies, in angstroms, the minimum allowed distance between atoms below which Close Contact is displayed.
This specifies, in angstrom, the maximum distance between hydrogen bond donor/acceptor pairs used in analyzing the number of possible hydrogen bonds when comparing rotamer conformations.
This specifies the increment of the side chain torsion (in degrees) used in the Spin Residue.
This specifies in angstroms the radius when Display Sphere tool is used.
This specifies the file containing side chain modeling and other protein modeling parameters.
This specifies the file containing data for the Karplus rotamer library.
When there are multiple possible conformations for the rotamer libraries, this tool enables you to step through them.
Save the current atomic coordinates to MSF
Restore the atomic coordinates from the MSF file.
Exit the Model Side Chain utility.