Protein-sol is a simple and free, web based suite of theoretical calculations and predictive algorithms for understanding protein solubility and stability.
The software can predict solubility based on the sequence properties of a protein, or given a structure, calculates the surface distribution of charge and hydrophocity as well as the predicted stability at 91 different pH and ionic strength combinations.
Protein-sol was built by the Warwicker group at the University of Manchester, with major contributions from Max Hebditch, Alejandro Carballo and Spyros Charonis, and hosted on a virtual machine provided by the Computational Shared Facility at the University of Manchester.
Please contact us at email@example.com if you have any questions, comments or further interest in using the tool.
Sequence solubility prediction software
Currently, the sequence prediction software will take a single amino acid sequence and return the result of a set of solubility prediction calculations, compared to a solubility database. These results are available for download in text form and are interpreted in graphs. See here for an example.
To run multiple sequences, the predictive algorithm is available for download.
Please use the following paper for citing the protein-sol sequence software
Building on work published in
Chan P, Curtis R, Warwicker J. Soluble expression of proteins correlates with a lack of positively-charged surface. Scientific Reports (2013)
Warwicker J, Charonis S, Curtis R. Lysine and Arginine Content of Proteins: Computational Analysis Suggests a New Tool for Solubility Design. Molecular Pharmaceutics (2014)
Patches and heatmap software
The patches and heatmap software calculates and visualises the distribution of charge, and hydrophobicity, across the protein surface. See here for an example of patches, and here for an example of heatmaps.
Given a protein PDB structure our in-house electrostatics software, using finite-difference Poisson–Boltzmann (FDPB) methods, calculates the distribution of potential across a surface, and can calculate the degree of surface patch hydrophobicity by comparing the ratio of non-polar to polar (NPP ratio) solvent accessible surface area (SASA) for all non-hydrogen atoms. The resulting surface properties are added to the PDB file in the B factor column, which can be viewed and manipulated on the Protein-sol website directly using the embedded NGL viewer, or locally in the user's preferred visualisation software.
For the potential display, the corresponding PDB file can be downloaded and viewed with approximately the same color scheme in PyMOL (The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC.) using the command.
spectrum b, red_white_blue, minimum=-86, maximum=86
For the non-polar / polar surface display, the corresponding PDB file can be downloaded and viewed with a similar color scheme in PyMOL (The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC.) using the command.
spectrum b, magenta_white_green, minimum=0.4, maximum=2.5
The paper describing our methods is
Building on work published in
Moutevelis E & Warwicker J. Prediction of pKa and redox properties in the thioredoxin superfamily. Protein science (2004)
Warwicker J. Improved pKa calculations through flexibility based sampling of a water-dominated interaction scheme. Protein Science (2004)
Bate P & Warwicker J. Enzyme/non-enzyme discrimination and prediction of enzyme active site location using charge-based methods. Journal of molecular biology, (2004)
Cole C & Warwicker J. Side-chain conformational entropy at protein-protein interfaces. Protein Science (2002)
Warwicker J. Simplified methods for pKa and acid pH-dependent stability estimation in proteins: removing dielectric and counterion boundaries. Protein Science (1999)
The NGL software is used under the MIT license, with fullscreen code adapted from here
AS Rose, AR Bradley, Y Valasatava, JM Duarte, A Prlić and PW Rose. Web-based molecular graphics for large complexes. 2016