SCWRL4 is based on a graph algorithm and potential function that results in good accuracy at high speed. This has been achieved through: (1) a backbone‑dependent rotamer library based on kernel density estimates; (2) averaging over samples of conformations about the positions in the rotamer library; (3) a fast anisotropic hydrogen‑bonding function; (4) a short‑range, soft van der Waals atom‑atom interaction potential; (5) fast collision detection using k‑discrete oriented polytopes; (6) a tree‑decomposition algorithm to solve the combinatorial problem; and (7) optimization of all parameters by determining the interaction graph within the crystal environment using symmetry operators of the crystallographic space group.
Accuracies as a function of electron density of the side chains demonstrate that side chains with higher electron density are easier to predict than those with low electron density and presumed conformational disorder. For a testing set of 379 proteins, 86% of χ1 angles and 75% of χ1+2 are predicted correctly within 40° of the X‑ray positions. Among side chains with higher electron density (25th–100th percentile), these numbers rise to 89% and 80%. The program maintains its simple command‑line interface, designed for homology modeling. To achieve higher accuracy, SCWRL4 is somewhat slower than SCWRL3 when run in the default flexible rotamer model (FRM) by a factor of 3–6, depending on the protein. When run in the rigid rotamer model (RRM), SCWRL4 is about the same speed as SCWRL3. In both cases, SCWRL4 will converge on very large proteins or protein complexes or those with very dense interaction graphs, while SCWRL3 sometimes would not.
SCWRL4.0 is free to researchers in non‑profit institutions. Obtaining SCWRL4.0 is fast and easy.
The non‑profit/academic license form is available here. Fill out the form and click I agree. You will see a page with your submitted data for verification; make sure to click Send request to complete the license request. Note: blank or clearly invalid requests will not receive a response.
Individuals in for‑profit institutions should contact Roland Dunbrack to obtain information on a commercial license for SCWRL4.0.
Installers for SCWRL4 are provided for the following operating systems:
The installation kits for each operating system have the following names, respectively:
install_Scwrl4_Linux (32‑bit) and install_scwrl4.0.2_64bit_2020_linux (64‑bit)install_Scwrl4_Mac-intel (32‑bit) and scwrl4.0.2_64bit_2020_macos.tar.gz (64‑bit)Scwrl4Installer.msi (32‑bit GUI); install_Scwrl4.0.4_32bit_2020_windows.exe (32‑bit command‑prompt); install_Scwrl4.0.4_64bit_2020_windows.exe (64‑bit command‑prompt)
Many operating systems still support 32‑bit executables; some dropped support of 32‑bit binaries. Download either 32‑bit or 64‑bit versions of SCWRL4 for your operating system.
Linux (32/64‑bit), macOS (32‑bit), and Windows command‑prompt installer (32/64‑bit)
Simply execute the file on the command line and follow the instructions. The program will ask for a location to install the program. Once installed, the program expects to find the rotamer library in the installation directory. To move the rotamer library, reinstall the software.
64‑bit macOS
The distribution is a .tar.gz (or .tar.xz) archive. Unpack it, for example:
tar -xvzf scwrl4_package_macos_2025.tar.gzConfigure SCWRL4:
source setup_scwrl4.sh
Open a new shell so you can execute Scwrl4 from any location.
Windows graphical installer (32‑bit)
Double‑click the installer and follow the directions. By default, it installs to C:\FCCC\Scwrl4. This is also where MolIDE expects to find SCWRL4. On some Windows platforms such as Windows 10, .NET 2.0 or .NET 3.5 may not be installed by default. If required, the GUI installer will prompt you to install .NET. You can obtain it:
scwrl4 -i input.pdb -o output.pdb > run.logRequired flags
-i <inputfilename> — Input PDB with required N, CA, C, O atoms-o <outputfilename> — Output PDB including predicted side‑chain coordinatesOptional flags
-f <framefilename> — PDB of ligand/neighboring coordinates used for steric checks-s <sequencefilename> — Sequence file specifying new sequence of fixed side chains-p <paramfilename> — Parameters file (overrides defaults)-h — Disable output of hydrogen atoms-t — Disable N‑terminal capping and OXT addition to C‑terminal residue-# — Calculate side‑chain conformations within the crystal (requires CRYST1)-i <inputfilename> [required]
The main input should be a protein backbone, with or without side chains, cofactors, or solvent. Residues with incomplete backbones are treated as glycines. Residues whose names do not match the standard 20 amino acids are also treated as glycines. The sequence is read from the first atom in each residue. To change the sequence, use the -s flag to supply a sequence file.
-o <outputfilename> [required]
The output file contains the identical backbone as the input file, with predicted coordinates for the side chains.
-f <framefilename> [optional]
Adds steric boundaries using a PDB file (cofactors, metals, lipids, another protein, etc.). The frame is fixed and used only for steric clash checks. Radii were determined from atom–atom distances in the PDB; all currently observed elements are supported.
-s <sequencefilename> [optional]
Sequence must have the same number of residues as the input backbone. Whitespace and numbers are ignored. Lower‑case letters indicate residues whose Cartesian coordinates should be left untouched (treated as fixed steric boundaries for the rest).
Examples
SDERYCNM — full SCWRL side‑chain replacementSdERYCNM — input residue (aspartate) left as isSxERYCNM — input residue (aspartate) left as is-p <paramfilename> [optional]
Specifies parameters for SCWRL4. The default file is set during installation; if not present there, SCWRL4 will look in the current directory and in the directory containing the executable. Options can be overridden using this flag.
-# [optional]
Performs calculation of side‑chain conformations within the crystal. Requires CRYST1 in the input file. SCWRL4 uses crystal symmetry to build coordinates of neighboring asymmetric units.
-h [optional]
Disables output of hydrogen atoms.
-t [optional]
Disables adding hydrogens to the N‑terminal nitrogen and adding the OXT atom to the C‑terminal residue for each chain.
Improved prediction of protein side‑chain conformations with SCWRL4.
G. G. Krivov, M. V. Shapovalov, and R. L. Dunbrack, Jr., Proteins: Structure, Function, and Bioinformatics (2009) 77(4):778–795.
Article
SCWRL4.0 is more accurate than SCWRL3. The table below gives the accuracy in χ1 and χ1+2 dihedral angles for a test set of 379 proteins. Accuracy is given for those side chains with electron density from the 25th–100th percentiles (see Shapovalov and Dunbrack, Proteins 66:279–303 (2007)). χ1 prediction accuracy is expressed as percent of side chains with χ1 dihedral angles within 40° of the X‑ray value. For χ1+2 to be correct, both χ1 and χ2 must be within 40° of their X‑ray values. Residue types are sorted by their SCWRL4.0 χ1 accuracy. For comparison, the accuracy of choosing rotamers based only on the maximum‑probability rotamer from the backbone‑dependent rotamer library is also given ("BBDEP").
| χ1 Prediction Accuracy | χ1+2 Prediction Accuracy | ||||||
|---|---|---|---|---|---|---|---|
| Residue Type | Num. of Residues | BBDep | SCWRL3 | SCWRL4.0 | BBDep | SCWRL3 | SCWRL4.0 |
| ALL | 45216 | 76.4 | 85.8 | 89.3 | 60.9 | 74.1 | 79.7 |
| ILE | 3043 | 93.3 | 96.5 | 98.6 | 76.2 | 86.1 | 90.9 |
| VAL | 3898 | 92.0 | 95.1 | 97.1 | — | — | — |
| PHE | 2115 | 76.2 | 94.8 | 96.9 | 71.7 | 89.9 | 94.8 |
| TYR | 1828 | 75.0 | 92.9 | 95.6 | 70.9 | 88.2 | 93.2 |
| LEU | 5096 | 75.8 | 93.0 | 95.4 | 70.8 | 87.2 | 91.0 |
| THR | 2935 | 89.8 | 92.1 | 94.0 | — | — | — |
| TRP | 758 | 72.7 | 86.5 | 93.0 | 49.3 | 69.5 | 83.0 |
| CYS | 805 | 75.0 | 90.8 | 92.7 | — | — | — |
| HIS | 1202 | 69.4 | 89.0 | 91.1 | 40.1 | 54.2 | 62.3 |
| ASN | 2238 | 71.4 | 85.2 | 90.1 | 56.3 | 67.0 | 74.9 |
| MET | 1107 | 70.6 | 84.6 | 89.0 | 46.9 | 71.6 | 79.0 |
| ASP | 3161 | 75.3 | 83.7 | 88.8 | 68.4 | 74.8 | 81.8 |
| PRO | 2489 | 84.0 | 84.9 | 88.2 | 80.4 | 81.6 | 84.7 |
| GLN | 1934 | 67.8 | 79.3 | 84.6 | 36.3 | 58.4 | 67.6 |
| LYS | 2996 | 70.3 | 78.8 | 81.9 | 54.5 | 66.7 | 69.6 |
| ARG | 2803 | 67.0 | 76.6 | 81.8 | 51.6 | 64.9 | 70.5 |
| GLU | 3579 | 65.5 | 74.9 | 78.3 | 44.5 | 56.8 | 63.8 |
| SER | 3229 | 66.0 | 69.6 | 75.8 | — | — | — |