Offers methods for structure prediction, design, and remodeling of proteins and nucleic acids. Rosetta provides a comprehensive software suite for modeling macromolecular structures. This resource permits users to: (i) understand macromolecular interactions, (ii) design custom molecules, (iii) develop ways to search conformation and sequence space, and (iv) find energy functions for various biomolecular representations.
Allows users to access and preprocess structural data for all kinds of life science research, and gives an immediate visual impression of the overall protein structure and contained ligand molecules. ProteinPlus contains a server for special interest to life scientists with an occasional need to work with protein structures thanks to six services addressing the most important tasks at the beginning of structure analysis (Protoss; PoseView; EDIA; SIENA; DoGSiteScorer; HyPPI). Users can choose an application service of interest, set additional tool configurations and start the calculation.
Permits to interactively visualize and analyse molecular structures and related data, including density maps, supramolecular assemblies, sequence alignments, docking results, trajectories, and conformational ensembles. UCSF Chimera allows users to incorporate new features. It contains some extensions which permits to visualize large-scale molecular assemblies such as viral coats, and allows researchers to share a Chimera session interactively despite being at separate locales. Other extensions can be used for extend the tool capabilities.
Allows prediction of binding poses. DOCK is a structure-based design program that is suited to address the issues for targeting RNA using physics-based scoring functions. The software can be employed for binding mode prediction for RNA–ligand complexes and can be useful in the drug design setting.
A package which approximates a complete search of the conformational, orientational, and positional space of the ligand in a given receptor. Glide offers the full range of quick and accurate options, from the HTVS to the SP. It also provides virtual screening, accurate binding mode prediction and universal applicability. Comparisons to published data on RMS deviations show that Glide is nearly twice as accurate as GOLD and more than twice compared to FlexX. Glide is also found to be more accurate than the Surflex method.
Allows users to detect similar small-molecule binding sites on proteins. PoSSuM is an online database that provides information related to over 49 million pairs of similar binding sites discovered among 5.5 million known and putative binding sites. It can be used for discovering novel opportunities for biological and pharmaceutical applications, such as predictions of functions and drug discovery.
Studies large virtual libraries of electrophilic small molecules. DOCKovalent exhaustively samples all poses and ligand conformations with respect to the covalent bond to the target nucleophile, constrained by ideal bond lengths and angles. DOCKovalent was used to prospectively screen compound libraries against three targets of therapeutic interest: AmpC β-lactamase, RSK2 kinase and JAK3 kinase. Multiple potent, reversible covalent inhibitors were found against all three targets. X-ray crystal structures of predicted ligands, and the occasional false negative, illuminated not only the method’s ability to prospectively identify ligands and to predict their structures, but also its limitations. Several of the new covalent ligands were tested in cell culture experiments that established biological efficacy and target engagement. To ensure that the method may be used by a broad community, it has been made available on an easy to use web server.
Performs comparative binding energy (COMBINE) analysis on a set of ligand-receptor complexes. gCOMBINE is the GUI developed as a wrapper to the original command-line COMBINE program. The software aims to derive informative quantitative structure-activity relationships. The software can be useful in several areas related to ligand binding, structure-activity relationships and drug design.
Makes the screening of millions of compounds across entire proteomes feasible. FINDSITE(comb) is an online service. It has virtual screening accuracy better than the best docking method under the challenging condition that no templates > 30% sequence ID to the target are present in the ligand binding databases. This method does not require experimental structure to give the best performance. For average 300 AA protein, FINDSITE(comb) can screen ten million compounds within 2 days on a single computer node.
Introduces a substantial improvement over classical scoring functions. RF-Score is a machine-learning scoring function that was constructed in an entirely data-driven manner by circumventing the need for problematic modelling assumptions via non-parametric machine learning. This method is particularly effective as a re-scoring function and can be used for virtual screening and lead optimization purposes.
Allows protein-ligand binding site (LBS) prediction. COACH is a consensus approach that combines the multiple prediction results of algorithms from TM-SITE, S-SITE, COFACTOR, FINDSITE and ConCavity. It was designed to combine the prediction results of TM-SITE and SSITE with other available LBS tools by the support vector machine (SVM) training.
Inherits both the speed of QVina 1 and the reliability of the original Vina. The efficacy of QVina 2 on the core set of PDBbind 2014 was tested. With the default exhaustiveness level of Vina (i.e. 8), a maximum of 20.49-fold and an average of 2.30-fold acceleration with a correlation coefficient of 0.967 for the first mode and 0.911 for the sum of all modes were attained over the original Vina.
Allows the researchers and scientists to perform protein-ligand covalent docking. In contrast to conventional molecular docking protocols, covalent docking will allow the formation of covalent linkages between the ligand and the receptor.
Determines ligand binding residues using 3D models of proteins. FunFOLD in based on cutting edge function prediction algorithms. It provides a graphical representation of the ligand-binding site, with predicted ligands and binding site residues highlighted. This tool creates a list of residues from the target sequences that are most likely to bind a ligand, along with a list of putative binding ligands.
Treats of efficient computational refinement of protein-small organic molecule complexes. The AMMOS2 web server aims to providing at the scientific community a free and user-friendly protein-ligand-water minimization tool. It offers the possibility for users to refine a large number of protein-ligand complexes after virtual screening. This tool proposes several solutions to assist docking and structure-based virtual screening experiments keeping in mind that water molecules mediating protein-ligand interactions are of key importance to design high-affinity hit molecules.
A web server dedicated to the docking of small molecules on target proteins. SwissDock aims at extending the use of protein-small molecule docking software far beyond experts in the field by providing convenient answers to many of the difficulties mentioned above. Predicted binding modes (BMs) can be viewed online with a simple embedded applet or analyzed in more details thanks to a seamless integration with the UCSF Chimera molecular viewer. The automatic setup of protein and ligand structures, the different parameter presets and the convenient visualization and analysis of docking predictions makes it accessible to a wide audience.
Elucidates 3D pharmacophores from a set of drug-like molecules that are known to bind to a target receptor. PharmaGist is a web application that searches for possible pharmacophores and reports the highest-scoring ones. This method detects pharmacophores common to subsets of input ligands. Its whole dataset consists of almost 80 crystal structures of receptor-ligand complexes. A downloadable version includes virtual screening capability.
Predicts ligand-binding sites. 3DLigandSite is a web server that uses ligands from similar structures to make predictions. Options are available to modify the display of the whole protein, predicted residues and ligands. The user can label the predicted residues making it easier for them to investigate the predicted binding site. Spacefill and wireframe options are also available for displaying the ligand cluster.
Compares a query pocket to known ligand binding pockets and predicts binding ligand molecules for the query. PatchSurfer2.0 recognizes pockets for the same ligand by identifying common local regions in pockets, even if the global folds of the proteins are different and the pockets do not share a common global shape. It also includes a feature that captures approximate patch position with a geodesic distance histogram.
Provides an intuitive interface for generating OPLS-AA/1.14*CM1A(-LBCC) force field (FF) parameters for organic ligands. LigParGen is a web server which generates ligand parameters for common simulation software packages such as NAMD, GROMACS, OpenMM, BOSS and MCPRO. The software allows the users to obtain high quality parameters for molecular mechanics (MM) simulations without extensive knowledge about MM force fields or quantum mechanics (QM) methods.