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.
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 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.
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.
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.
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.
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.
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.
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.
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.
Integrates ligand similarity by Tanimoto coefficient and receptor similarity by protein structure alignment program SPalign. SPOT-Ligand was found to yield a consistent performance in DUD and DUD-E docking benchmarks even if model structures were employed. It improves over docking methods (DOCK6 and AUTODOCK Vina) and has a performance comparable to or better than other binding-homology methods (FINDsite and PoLi) with higher computational efficiency.
Converts g IC50 to Ki values for inhibitors of enzymes and of protein-ligand interactions. IC50-to-Ki converter is a web server that calculates Ki values from IC50 values using equations for enzyme-substrate and target-ligand interactions by different inhibitory mechanisms. The software provides results for classic and tight-binding inhibitors of enzyme activity and ligand-binding reactions that are assumed to follow relatively simple kinetic schemes. It aims to facilitate research and the development of potential therapeutic products.
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.
Maps sequence variants to protein structures from the Protein Data Bank (PDB), and further to protein–protein, protein–nucleic acid, protein–compound, and protein–metal ion binding sites. GenProBiS enables detection of sequence variants within a protein binding site. It allows visual exploration of interactions, or loss of interactions, of a specific mis-sense mutation with a specific ligand. The tool permits focused laboratory experiments based on targeted hypotheses in several research fields including human, veterinary medicine, animal and plant breeding.
A web service for fully automated detection and visualization of relevant non-covalent protein-ligand contacts in 3D structures. PLIP stands out by offering publication-ready images, PyMOL session files to generate custom images and parsable result files to facilitate successive data processing. Furthermore, the availability of PLIP source code enables local batch processing, customization of the algorithm for special applications as well as active development of the tool in the community.
A web server for prediction of ligands based on detected local structural similarities in proteins. ProBiS-ligands requires a query protein structure or a query binding site, and this is first compared to proteins in the nr-PDB using the local structural alignment algorithm ProBiS, resulting in a list of similar representative protein structures that share similar 3D amino acid environments with the query protein. ProBiS-ligands provides an interactive environment in which users can explore the predicted protein–ligand complexes. One of the major advantages of ProBiS-ligands is that it allows transposition of ligands between protein structures irrespective of protein folding and with no prior knowledge of binding sites.
Predicts binding sites of non-metal ligands. GalaxySite is a web server that employs molecular docking. Binding ligand is predicted using a similarity-based method, and the protein structure is provided by user or predicted from a template-based modeling method. The method is applicable to experimentally resolved structures, model protein structures and protein sequences. The software predicts specific binding ligands and binding poses, which can be useful for further applications, e.g. in computer-aided drug discovery.
Provides a web server for the prediction of phosphate binding sites in protein structures. The Phosfinder server offers a user-friendly version of the Pfinder method, enriched with the possibility to visualize the predicted phosphate binding sites on the query structure. It predicts the actual coordinates where the phosphate group is located, as opposed to a generic surface region. Moreover, the specific amino acids that bind phosphate are also predicted.
Extracts structural templates of protein binding sites from the latest release of Protein Data Bank (PDB). Protemot is a web server equipped with an automatic mechanism designed for prediction of protein binding sites. The mechanism employed to expedite the analysis process matches the tertiary substructures on the contour of the query protein with the templates in the library. Because of the automatic extraction mechanism, Protemot's template library contains many entries.
A web service enabling drug developers to carry out network pharmacology-based prediction and analysis by integrating results from structural biology with systems biology. Its user-friendly GUI interface simplifies essential operations for large-scale screening. Using the predictive docking approach, systemsDock can test a large number of target proteins with good prediction accuracy. This will reduce the number of tests for bioassay. Together with a curated pathway map, systemsDock helps to comprehensively characterize the underlying mechanism of a drug candidate and to interpret its cascading effects, improving the prediction of drug efficacy and safety.
A web service for identification of ligand & residue interactions, SNP and pathway analysis. Manoraa allows the users to input the chemical fragments and present all the unique molecular interactions to the target proteins with available three-dimensional structures in the PDB. The users can also link the ligands of interest to assess possible off-target proteins, human variants and pathway information using our all-in-one integrated tools. Taken together, we envisage that the server will facilitate and improve the study of protein–ligand interactions by allowing observation and comparison of ligand interactions with multiple proteins at the same time.
Uses a combination of stochastic and deterministic search techniques to generate low energy ligand poses. rDock generate a single ligand pose uses 3 stages of Genetic Algorithm search (GA1, GA2, GA3), followed by low temperature Monte Carlo (MC) and Simplex minimization (MIN) stages. It can recognize nine feature types: neutral hydrogen bond acceptor, neutral hydrogen bond donor, hydrophobic, hydrophobic aliphatic, hydrophobic aromatic, negatively charged, positively charged, and any heavy atom.
Assists users in virtual screening. FLAP is able to perform “lead-hopping” or “scaffold-hopping” into different chemical classes, making it valuable alongside 2D similarity methods. It can automatically select optimal templates by training the scoring function. Moreover, this tool can be applied for investigating several situations, including docking, alignment, pharmacophore hypothesis elucidation, and 3D QSAR.
Creates a target-specific scoring functions to address the limited affinity prediction of general-purpose scoring functions. AutoShim defines and evaluates specific interactions between a bound ligand and a protein active site. It combines medium-throughput screening of an initial designed set of 10 000 kinaphiles. The tool approaches the best 2D-QSAR and should be that much more useful for scaffold hopping.
Allows easy analysis and interpretation of protein–ligand interaction data. OOMMPPAA includes protein–ligand activity data with protein–ligand structural data utilizing 3D matched molecular pairs. It is useful to investigate interesting structure–activity relationships (SAR) within such large data sets. The tool summarizes the data for a large data set in a clear and intuitive way and highlights interesting SAR in the context of the protein binding site.
Computes small molecules’ torsional potential energies. H-TEQ can be used for the quantification of the hyperconjugation energy based on the electronegativity of atoms. It allows users to analyze the influence of different stereoelectronic effects on the torsional rotation. This tool was applied on different molecules such as: ammonium derivatives, phosphonium derivatives, aminoborane derivatives and monosaccharides.
Evaluates protein-ligand interactions based on compatibility of local molecular surfaces. PL-PatchSurfer is a structure-based virtual screening (SBVS) program that ranks ligands in a library for a target pocket by identifying complementarity between pocket and ligand local surface regions. The software uses a molecular surface representation. It can extend the capability of virtual screening by providing accurate predictions in difficult cases, such as scaffold hopping or cases where only apo form of targets or template-based models of targets are available.
Generates energy-optimized pharmacophores. e-pharmacophores is based on mapping of the energetic terms from the Glide XP scoring function onto atom centers. It was tested by screening a set of 30 diverse crystal structures of pharmaceutically relevant protein targets and present database enrichments. The tool attempts to take a step beyond simple contact scoring by incorporating structural and energetic information.
Analyzes and identifies binding sites, and predicts target druggability. SiteMap studies the druggability of proteins as measured by their ability to bind passively absorbed small molecules tightly. For helping users, this tool supplies several contents and graphical information. These data helps to modify ligand structure to enhance potency or improve physical properties in a lead-optimization context or assess virtual hits in a lead-discovery application.
Offers solution for pharmacophore perception, quantitative structure-activity relationship (QSAR) model development, and 3D database screening. PHASE aims to suggest a set of plausible models that can be evaluated by various criteria whose relevance is assessed by the user. It is able to reproduce crystallographic pharmacophores. The tool extracts orthogonal latent factors from a data matrix by using a standard recursive procedure. It can efficiently classify a large test set of inhibitors into three activity categories.
Facilitates the analysis and interpretation of protein–ligand interaction data. WONKA is able to analyse ensembles of protein–ligand structures and to find trends within a set of structures of the same protein. It summarizes large ensembles of protein–ligand structures of the same protein target. The tool offers a platform to annotate and share data within and between research groups.
Allows flexible ligand docking. Idock is a virtual screening tool that consists of two basic components: a scoring function to predict the binding affinity, and an optimization algorithm to explore the conformational space. The software has built-in support for virtual screening, searches for ligands in a user-specified folder and docks them one by one. It also reuses threads and grid maps across multiple ligands. It is capable of screening 1.3 drug-like ligands per CPU minute on average.
A freely available R/Bioconductor package for complex molecular representation from drugs, proteins and more complex interactions, including protein-protein and compound-protein interactions. Rcpi could calculate a large number of structural and physicochemical features of proteins and peptides from amino acid sequences, molecular descriptors of small molecules from their topology and protein-protein interaction and compound-protein interaction descriptors. In addition to main functionalities, Rcpi could also provide a number of useful auxiliary utilities to facilitate the user's need.
An efficient software tool for identifying ligand binding-sites and predicting pseudo ligand corresponding to each binding site identified. AutoSite identifies ligand-binding sites with higher accuracy than other leading methods, and produces fills that better matches the ligand shape and properties, than the fills obtained with AutoLigand software.
A web app designed for analysis and visualization of hydrophobic/hydrophilic properties of biomolecules supplied as 3D-structures. Furthermore, PLATINUM provides a number of tools for quantitative characterization of the hydrophobic/hydrophilic match in biomolecular complexes e.g. in docking poses. These complement standard scoring functions. The calculations are based on the concept of empirical molecular hydrophobicity potential (MHP).
Gives a heuristic solution to a computationally hard problem (NPC). CombDock is an algorithm for the automated assembly of protein substructures. This application is able to predict near-native assemblies for various examples of both domains and to build blocks with different levels of distortion. It can also be used in protein structure prediction if the local structural units are given and assist in obtaining a structural model.
Receptor-ligand interactions are a central phenomenon in most biological systems. aCSM is a graph-based-binding pocket signature that proved to be efficient and effective in handling large-scale protein ligand prediction tasks.
A server for ligand binding site analysis in protein structures. SiteComp uses molecular interaction fields (MIFs) as descriptors of small molecule ligand binding sites. MIFs describe the spatial variation of the interaction energy between a target molecule and a probe, which represents a specific chemical group or atom. SiteComp provides three types of MIF-based analyses: (i) binding site comparison; (ii) binding site decomposition and (iii) multi-probe characterization.
Allows for protein mutant modeling and the docking ligand molecules into them. TRITON can be used to investigate mechanisms of protein–ligand interactions and to assess the role of individual residues in the binding. It provides graphic tools for the preparation of the input data files, for running calculation and for the analysis of the output data. The tool is helpful not only for computational chemists but also for experimentalists providing assistance and direction in preparation of laboratory work.
A webserver designed to answer questions that previously required several independent queries to diverse data-sources. It also performs basic manipulations and analyses of the structures of protein-ligand complexes. The LigDig webserver is modular in design and consists of seven tools, which can be used separately, or via linking the output from one tool to the next, in order to answer more complex questions. Currently, the tools allow a user to: (i) perform a free-text compound search, (ii) search for suitable ligands, particularly inhibitors, of a protein and query their interaction network, (iii) search for the likely function of a ligand, (iv) perform a batch search for compound identifiers, (v) find structures of protein-ligand complexes, (vi) compare three-dimensional structures of ligand binding sites, and (vii) prepare coordinate files of protein-ligand complexes for further calculations.