Scwrl

Servers

Software

Libraries

SCWRL4

Prediction of protein side-chain conformations

SCWRL4 is based on a new algorithm and new potential function that results in improved accuracy at reasonable speed. This has been achieved through: 1) a new 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 chi1 angles and 75% of chi1+2 are predicted correctly within 40 degrees of the X-ray positions. Among side chains with higher electron density (25th-100th percentile), these numbers rise to 89% and 80%. The new 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.

License

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. Just click and then fill out the form and click "I agree". You will get a page with your submitted data for you to check. Then make sure you hit "Send request" to complete the license request. Note: if you submit a blank request or nonsense information, you will not get a response from us.

Individuals in for-profit institutions should contact Roland Dunbrack to obtain information on a commercial license for SCWRL4.0.

Availability and Installation

Installers for SCWRL4 are provided for the following operating systems:

Linux (32-bit and 64-bit)
Apple macOS (32-bit and 64-bit) -- Catalina or version 10.15+ requires 64-bit
Microsoft Windows 10 / 8 / 7 / Vista / XP (32-bit and 64-bit)

The installation kits for each operating system have the following names, respectively:

install_Scwrl4_Linux (32-bit)
install_scwrl4.0.2_64bit_2020_linux (64-bit)
install_Scwrl4_Mac-intel (32-bit)
scwrl4.0.2_64bit_2020_macos.tar.gz (64-bit)
Scwrl4Installer.msi (32-bit installer with a graphical interface)
install_Scwrl4.0.4_32bit_2020_windows.exe (32-bit command-prompt installer)
install_Scwrl4.0.4_64bit_2020_windows.exe (64-bit command-prompt installer)

Many operating systems still support 32-bit executables; some droppped support of the 64-bit binaries. Download either 32-bit or 64-bit versions of Scwrl4 for your operating system:

Linux (32/64 bits), macOS (32 bits) and
Windows Command-Prompt Installer (32/64 bits)
Simply execute the file on the command line and follow the instructions. The program will ask for a location to install the program in. Once installed, the program will expect to find the rotamer library in the installation directory. In order to move the rotamer library, reinstall the software.

64-bit macOS
The distribution is a tar.gz archive. Unzip it with
tar -xvzf scwrl4.0.2_64bit_2020_macos.tar.gz

Configure Scwrl4 with
source Configure_Scwrl4_1st_time.script

Please re-open a new shell terminal so that you will be to execute Scwrl4 with a simple Scwrl4 command from any location on your disk.

Windows Graphical User Interface (GUI) Installer (32 bits)
Just double-click the installer file and follow the directions. By default, it will place the program in C:\FCCC\Scwrl4. This is also where BAM or MolIDE expect to find SCWRL4. The installation is complete. On some Windows platforms such as Windows 10, .NET 2.0 or .NET 3.5 are not installed by default. If it is the case, the GUI installer will complain and ask to install the .NET component. You can install it:

either by downloadning the official .NET 3.5 component from our website (the link will be be provided during the licensing)
or from the official Microsoft website
or from within Windows OS itself (recommended for Windows 10) by following these instructions from the official Microsoft website.

Usage

scwrl4 −i inputpdbfilename −o outputpdbfilename > logfilename

Required flags:
-i <inputfilename> Input file in PDB format of required N,CA,C,O atoms
-o <outputfilename> Output file in PDB format including predicted side-chain coordinates

Optional flags:
-f <framefilename> Input file in PDB format of ligand coordinates (see below for format)
-s <sequencefilename> Sequence file for specifying new sequence of fixed side chains
-p <paramfilename> Input file of parameters
-h Disable output of hydrogen atoms
-t Disable capping of N and C terminal residues with HN and OXT atoms
-# Calculate side-chain conformations of crystal

-i <inputfilename> [required]
The main input file to scwrl should be a protein backbone, with or without sidechains, cofactors, or solvent. Residues with incomplete backbones are treated as glycines. Residues with names that do not match the standard 20 amino acid names are also treated as glycines. The sequence of residues is read from the first atom in each residue. If you wish to change this sequence, the -s flag allows you to enter a new sequence independently.

-o <outputfilename> [required]
The output file contains the identical backbone as the input file, with predicted coordinates for the sidechains.

-f <framefilename> [optional]
This file is used to add additional steric boundaries to the sidechains. It should be in pdb format, and might contain cofactors or metal atoms, lipid molecules, or another protein. In any case, it is held fixed and used only for steric clash checks.Radii were determined from atom-atom distances in the PDB. All elements currently observed in the PDB can be treated by scwrl.

-s <sequencefilename> [optional]
This flag is followed by a sequence file. The sequence should have the same number of residues in it as the input backbone. White space, carriage returns, and numbers are ignored. Lower-case letters in the sequence indicate that the Cartesian coordinates for the corresponding residues are to be left untouched, and will be treated as steric boundaries only for the other side chains.

Examples:
SDERYCNM - full SCWRL side-chain replacement
SdERYCNM - input residue (aspartate) is left where as is.
SxERYCNM - input residue (aspartate) is left where as is.

-p <paramfilename> [optional]
File that specifies parameters for SCWRL4. The default file is set during installation; if it is not present in that location, SCWRL4 will look in the current directory and in the directory where the executable is located. These options can be overridden using this flag.

-# [optional]
Perform calculation of side-chain conformations within the crystal. Requires CRYST1 record in inputfilename. SCWRL4 uses crystal symmetry to build backbone and side-chain coordinates of asymmetric units neighboring the input coordinates.

-h [optional]
Disables the output of hydrogen atom coordinates.

-t [optional]
Disables adding hydrogens to the N-terminal nitrogen atom. By default, only a residue numbered 1 will be treated as N-terminal. Disables addition of OXT atom to C-terminal residue for each chain.

Article

Improved prediction of protein side-chain conformations with SCWRL4.
G. G. Krivov, M. V. Shapovalov, and R. L. Dunbrack, Jr., Proteins: Structure, Function, Bioinformatics 2009, 77(4): 778-795. Article

Accuracy

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 crystallographic 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 just based on the rotamer with maximum probability 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	----	----	----