CAVER Web 1.0
Caver Web is an interactive web server for comprehensive analysis of protein tunnels and channels as well as the ligands’ transport within a single graphical user interface. The whole process of tunnel detection and analysis of ligand transport is facilitated by automated guidance procedures which assist the users to correctly set up the calculation leading to accurate and biologically relevant results. The first part of the workflow is tunnel detection and visualization using the gold standard Caver. The second part of the workflow analyses the ligand transport by CaverDock. Multiple ligands can be provided as the files with coordinates, ZINC database accession codes or by drawing the structure in molecule editor. CaverDock balances computational demands (2-20 min/job) and accuracy.
SoluProt is a web application for a prediction of protein solubility from protein primary sequence. A solubility score calculated for an entire protein sequence is useful for the prioritization of protein sequences selected for the laboratory production in genomic projects. The predictor is in its current version based on the random forest regression model and employs 36 sequence-based features, e.g., amino acid content, predicted disorder, alpha-helix and beta-sheet content, sequence identity to PDB and several aggregated physico-chemical properties. SoluProt currently achieves the accuracy of 58.2% and is a subject to further active development.
EnzymeMiner is a web application for automated and periodical mining of interesting sequences in genomic databases. The server utilizes a number of sequence and structural bioinformatics tools for the identification of protein-coding genes with conserved catalytic residues presumably catalyzing a defined enzymatic reaction. The functional diversity of mined hits is secured by the prediction of protein tertiary structures, analysis of protein cavities and access tunnels, modelling of enzyme-substrate complexes and prediction of their reactivity.
CalFitter is a computational tool for an analysis and fitting of calorimetric protein melting curves obtained from differential scanning calorimetry (DSC) measurements. The application allows simultaneous global fitting with various scan rates and reheating using 10 different models of unfolding. Apart from the heat capacity curve, each model provides population of intermediates versus temperature, fitted parameter values, and respective confidence intervals of the fitting. The program provides a means to export the analysis into Excel as well.
CaverDock is a new tool for an extremely rapid analysis of transportation processes in proteins. It models the transportation of a ligand (a substrate, a product, an inhibitor, a co-factor or a co-solvent) from the outside environment into the binding site and vice versa. The tool implements a novel algorithm based on molecular docking and is able to produce contiguous ligand trajectories and estimations of the binding energy along the pathways. CaverDock uses Caver for the pathway identification and a heavily modified Autodock Vina as the docking engine. The tool is much faster than molecular dynamics (2-20 min per job) and is also suitable for virtual screening.
FireProt provides a robust computational strategy for predicting highly stable multiple-point mutants. It combines energy- and evolution-based approaches with smart filtering to identify additive stabilizing mutations. FireProt integrates sixteen computational tools, utilizing both sequence and structural information. The web server provides users with a one-stop-shop solution for the design of thermostable proteins, designed by three strategies: (i) an evolution-based approach, utilizing a back-to-consensus analysis; (ii) an energy-based approach, using conservation, correlation, and energy and (iii) a combined approach.
PredictSNP1 is an ensemble-based classifier for a prediction of the effect of amino acid substitutions and their prioritization for experimental characterization. It combines six well-established computational methods (MAPP, PhD-SNP, PolyPhen-1, PolyPhen-2, SIFT, SNAP) with a two-level weighted consensus approach to provide a more accurate and robust alternative to the predictions delivered by the individual tools. The predictions are complemented with experimental annotations from the Protein Mutant and the UniProt databases.
PredictSNP2 extends the scope to nucleotide substitutions and enables the identifications of disease-related variants within the whole genome. Similarly to PredictSNP1, the results of the five existing best-performing tools (CADD, DANN, FATHMM, FunSeq2 and GWAVA) are combined with two-level weighted consensus approach. To provide a comprehensive evaluation of variants, the predictions are complemented with annotations from eight databases.
HotSpot Wizard 3.0
HotSpot Wizard is a web server for an automated identification of ‘hot spots’ and a design of smart libraries for engineering protein stability, catalytic activity, substrate specificity and enantioselectivity. HotSpot Wizard implements four different established protein engineering strategies, enabling users to selectively target sites affecting the protein stability and catalytic properties. The server should be useful for protein engineers interested in exploring the structure of their favourite protein and for the design of mutations in site-directed mutagenesis and focused directed evolution experiments.
CAVER is a gold standard for an identification and characterization of tunnels and channels in macromolecular structures. The new version enables an automatic analysis of transport pathways in large ensembles of protein conformations. The analysis of molecular dynamics simulation is essential for the estimation of pathway characteristics and the elucidation of the structural basis of tunnel gating. CAVER paves the way for the study of important biochemical phenomena in the areas of molecular transport, molecular recognition and enzymatic catalysis. The software is available as a multiplatform JAVA command-line application or a PyMol plug-in.
CAVER Analyst 2.0
CAVER Analyst is a tool for a calculation, analysis and real-time visualization of access tunnels and channels in static and dynamic protein structures. It provides an intuitive graphic user interface for setting up the calculation and an interactive exploration of identified tunnels/channels and their characteristics. Novel integrated algorithms allow for an efficient analysis and data reduction in large protein structures and molecular dynamics simulations in AMBER, GROMACS and CHARMM formats. It offers a possibility to design one or more mutations in selected positions. CAVER Analyst is a freely available multi-platform software written in JAVA.