Handles and searches large virtual combinatorial libraries. FTrees performs similarity searches in the generated Fragment Space. It stores the physicochemical properties of the substructure represented by a node in a property profile for that node. This tool is able to select that topology-preserving mapping belonging to the best matching overlay of two molecules both represented by their corresponding Feature Trees.
Superposes pairs of molecules and takes full flexibility of one of the structures into account. FlexS serves for superimposing pairs of ligands, one of which is treated as flexible (test ligand) and is placed onto the other ligand which is treated as a rigid structure (reference ligand). This tool allows users to (1) screen databases of considerable size and (2) to analyze a single superposition in detail.
Determines the interaction strength between two bound molecules of a given orientation. DockoMatic eases set-up, calculation, and result analysis for large numbers of docking jobs. It permits users to construct a library of mutated peptides for docking to a multi-subunit protein receptor without manually generating the mutated peptide structures. This tool is useful for drug repurposing.
Builds small 3D compounds. Frog can construct single or ensembles of low to medium energy 3D conformations starting from a 1D/2D or 3D given structure. It clarifies compound stereochemistry including chiral sites with a user-defined maximum number of generated conformers. This tool is useful for in silico studies, such as ligand-based or structure-based virtual screening; or lead compounds optimization.
Allows users to guide the Scaffold Hopping procedure during the drug discovery process. SHOP is a program that substitutes one part of a molecule with another one and retains their pharmacophoric interaction points. Moreover, this tool can maintain 3D interaction capabilities, consider the synthetic feasibility and the ADME profiles of the potential candidates.
Offers a platform dedicated to the screening of proteins for ligand docking. SLIDE investigates ligand candidates into the binding site of the target protein by using distance geometry. It can be used for: (i) matching interactions made by previously known ligands with a specific protein; (ii) docking using unbiaised or merged templates or ligand conformers; (iii) generating interaction tables for matchprint analysis.
A web-oriented peptidomimetic compound virtual screening tool based on a multi-conformers three-dimensional (3D)-similarity search strategy. Key to the development of pepMMsMIMIC has been the creation of a library of 17 million conformers calculated from 3.9 million commercially available chemicals collected in the MMsINC(R) database.
Performs ligand-based screening using a 3D molecular similarity engine. wwLigCSRre provides an online versatile facility to assist the exploration of the chemical similarity of families of compounds. It also proposes some scaffold hopping from a query compound. This tool allows the user to screen several chemically diversified focused banks, such as Kinase-, CNS-, GPCR-, Ion-channel-, Antibacterial-, Anticancer- and Analgesicfocused libraries.
A USRbased webserver for large-scale prospective virtual screening. USR-VS performs large-scale ligand-based Virtual Screening (VS), which is oriented to the prospective validation of the obtained results. It provides interactive visualization of the similarity of the query molecule against the hit molecules as well as vendor information to purchase selected hits in order to be experimentally tested.
Streamlines the steps of performing a virtual screening and analyzes results. Raccoon is a graphical user interface (GUI) that includes (i) automated server connection manager and installation of docking services, (ii) ligand library for upload and management of large ligand collections, (iii) receptor management from multiple targets and flexible residues, (iv) graphical management of jobs on computational resources, (v) automated retrieval and preprocessing of results to extract features of interest, and many others.
Provides an online, interactive environment for the virtual screening of large compound databases using pharmacophores, molecular shape and energy minimization. Users can import, create and edit virtual screening queries in an interactive browser-based interface. Queries are specified in terms of a pharmacophore, a spatial arrangement of the essential features of an interaction, and molecular shape. Search results can be further ranked and filtered using energy minimization. In addition to a number of pre-built databases of popular compound libraries, users may submit their own compound libraries for screening. Pharmit uses state-of-the-art sub-linear algorithms to provide interactive screening of millions of compounds. Queries typically take a few seconds to a few minutes depending on their complexity. This allows users to iteratively refine their search during a single session. The easy access to large chemical datasets provided by Pharmit simplifies and accelerates structure-based drug design.
Aids the computational identification of small-molecule ligands. NNscore is based on a neural-network scoring function and provides a single estimate of the pKd. It attempts to simulate, albeit inadequately, the microscopic organization of the brain. The tool can be used to successfully characterize the binding affinities of protein-ligand complexes. It appears that its major strength is largely orthogonal to other kinds of functions based on force fields, linear regression, and statistical analyses.
A multi-objective genetic algorithm for the generation of conformer ensembles. Balloon creates 3D atomic coordinates from molecular connectivity via distance geometry and conformer ensembles. The input can be SMILES, SDF or MOL2 format. Output is SDF or MOL2. Flexibility of aliphatic rings and stereochemistry about double bonds and tetrahedral chiral atoms is handled.
Enables any user to estimate polypharmacology profiles and side effects of compounds based on the molecular similarity concept. ElectroShape is a method that compares the distance and charge distributions of a molecule from 4 different surrounding points, which allows its 3D similarity to other molecules to be assessed in a very fast and efficient way. In addition, the calculated molecular descriptors can be stored for further use, which speeds up subsequent searches. ElectroShape provides a significant addition to the family of ultra-fast ligand-based virtual screening methods, and its higher-dimensional shape recognition approach has great potential for extension and generalisation.
Provides a graphical user interface for the virtual screening (VS) of chemical libraries integrated within a relational database. VSDMIP implements a visual interface for managing the most common tasks in VS. The software allows users to execute both structure-based VS (SBVS) and ligand-based VS (LBVS) protocols, or any combination of the two, by means of a GUI implemented in the PyMOL molecular graphics program.
Provides biologically relevant molecular alignments of the ligands. mRAISE is a tool for ligand-based virtual screening based on the RApid Index-based Screening Engine (RAISE) technology. The triangle-descriptor abstraction of small molecules allows fast non-sequential screening of millions of compounds. Calculated alignments are scored using a Gaussian-type scoring function which scores the general shape overlap as well as the compatibility of physicochemical features of aligned molecules.
Enables automatic comparison of RMDS-based molecular docking performances of different docking/scoring methods. MMsDockBench is a platform that automates the procedure from the setup of docking benchmarks to virtual screening (VS) campaigns. The software can assist users in identifying the best docking/scoring combination to perform a docking-based VS campaign.
Automates docking jobs with AutoDock. DOVIS is a utility software and a Linux cluster-based application that can reliably screen millions of compounds against a receptor and automatically save the top percentage of high-scoring hits. It runs in parallel on hundreds of central processing units (CPUs) and docks large numbers (millions) of ligands to a target receptor. It also automatically partitions input ligands, prepares parameter files for AutoDock, launches parallel AutoDock runs, parses results, and saves a set of top-ranking docked ligands.
Generates computational models from user-defined small molecule datasets based on structural features identified in hit and non-hit molecules in different screens. Each new model is applied to all datasets in the database to classify compound specificity. MolClass thus defines a likelihood value for each compound entry and creates an activity fingerprint across diverse sets of screens. MolClass uses a variety of machine-learning methods to find molecular patterns and can therefore also assign a priori predictions of bioactivities for previously untested molecules.
Creates in silico simulated high throughput screening data sets for use in testing and selecting appropriate statistical techniques for quality determination and hit identification. NoiseMaker can be useful for broader comparisons of available hit identification methods. This simulation software offers two main features: (i) the ability to generate a random set of ‘true hits’ that conform to expected characteristics and (ii) the ability to apply user-specified noise to a list of true hits to model realistically messy screening results.
Allows large-scale ligand-based Virtual Screening (VS). HybridSim-VS combines two-dimensional (2D) fingerprint- and tri-dimensional (3D) shape-based similarity search methods. It is a general hybrid molecular-similarity protocol. The tool was tested against a standard database of active and decoy molecules for 40 pharmaceutically relevant protein targets in the Database of Useful Decoys-Enhanced (DUD-E). It allows users to further analyze VS results.
Performs extensive sampling of a G protein-coupled receptors (GPCRs) and ligand conformation. LDM is a process that integrates a combination of scoring functions used to prioritize complexes for further sampling. It simplifies overcoming energy barriers and focuses the conformational search in the relevant space. To work, this tool requires only a single known ligand for the GPCR to undergo its refinement.
Consists of an integrated bioinformatics and chemoinformatics web-resource dedicated to adenosine receptors. Adenosiland creates a virtual space where simultaneously analyze sequence and structural information assigned to all cloned adenosine receptors. The software provides several structure-based and ligand-based query functions for facilitating the exploration of adenosine receptor structures from primary sequences to three-dimensional architectures.
Provides a solution to the lack of atom type information in the ultrafast shape recognition (USR) algorithm. Researchers, particularly those with only limited resources, who wish to use ligand-based virtual screening in order to discover new hits, will benefit the most. Online chemical databases that offer a shape-based similarity method might also find advantage in using USRCAT due to its accuracy and performance. The source code is freely available and can easily be modified to fit specific needs.
Offers a cost-effective way to identify and order new drug candidates has been recently launched. mcule provides a comprehensive, carefully curated database of molecules immediately available for virtual screening. It provides a convenient, online solution for managing compound databases and libraries as molecule collections. The user can keep track on all the previous compound selections and get back to start the compound ordering process whenever it is necessary.
Allows to evaluate protein-ligand binding. MedusaScore is a scoring function that describes the protein-ligand binding using physical interaction model. The function includes an explicit hydrogen-bonding model and EEF1 pairwise implicit solvent model, which allows accurate modeling of the hydrogen-bonding and desolvation effect without large-scale molecular dynamics (MD) simulations. Since the MedusaScore does not rely on parameter training using protein-ligand binding data, it is transferable to targets and small molecules beyond the tested datasets.
Uses 3D molecular fields to make particularly suitable for scaffold hopping. Blaze is a ligand based virtual screening tool. It helps to: (i) increase the diversity of project leads and backups, (ii) jump into new areas of chemical space, (iii) improve the lead-like properties of hits, (iv) virtually screen 10 million structures in a few hours, and (v) design diverse libraries of compounds for synthesis or biological screening.
Ranks databases of chemical compounds. LigMatch is a virtual screening (VS) method which uses a geometric hashing method to compare database compounds with the 3D bioactive conformation of a template ligand. The software can perform in the absence of 2D similarity to the template ligands. It could also be applied to protein targets for which no crystal structure with a bound inhibitor is available, by using low-energy conformations of known actives as the template ligands.
Allows covalent docking and virtual screening in molecular operating environment (MOE). DOCKTITE combines the knowledge-based scoring function drug score extended (DSX) and the empirical scoring functions implemented in MOE. The software can differentiate binders from nonbinders and rank active compounds regarding their experimentally determined binding affinity values in a congeneric series of ligands. It is a useful workflow for large-scale virtual screening purposes and can aid at all stages of a modern drug development process.
Performs virtual screening (VS). PoLi is a pipeline that (i) detects binding pockets in the query protein structure, (ii) identifies similar pockets in the holo-template library, (iii) copies ligands from similar pockets and (iv) subsequently uses them for ligand-based virtual screening. VS is performed using a combination of 2D fingerprint based and 3D-shape based similarity metrics.
Allows discovery of 2D and 3D similarities between pairs of molecules. LiSiCA is a ligand-based virtual screening software that uses a maximum clique algorithm, a reference compound and a database of target compounds. The software was used for identification of new potentials inhibitors of butyrylcholinesterase, an anti-Alzheimer target. It is able to determine two dimensional or three dimensional similarities between compounds.
Consists of a rational ligand/structure shape-based virtual screening approach. SABRE is a program that combines ligand shape-based similarity SABRE and the 3D shape of the receptor binding site. The program can be useful for the identification of active compounds that are similar to reference molecules and the prediction of activity against other targets. Its performance were assessed using he Database of Useful Decoys (DUD) and the filtered version (WOMBAT) of 10 DUD targets.
A web tool for rapid ligand-based virtual screening (LBVS) of small to ultralarge libraries of small molecules. SwissSimilarity offers the possibility to perform LBVS on more than 30 chemical databases which list drugs, bioactive and commercial molecules, as well as 205 million of virtual compounds readily synthesizable from commercially available synthetic reagents. Predictions can be carried out on-the-fly using six different screening approaches, including 2D molecular fingerprints as well as superpositional and fast nonsuperpositional 3D similarity methodologies. User interface and backend have been designed for simplicity and ease of use, to provide proficient virtual screening capabilities to specialists and nonexperts in the field.
Allows users to obtain alignment-independent 3D quantitative structure-activity relationships. Pentacle begins from a set of features and calculates relevant 3D maps of interaction energies between the molecule and chemical probes. It can encode these maps into GRID Independent Descriptors (independant of the alignment of the series). Moreover, this program is able to construct a model and guide users through the extracting of different information.
Creates conformers with a prebuilt library of fragments and a knowledge base of torsion angles. OMEGA can sample the conformational space around solid-state structures of druglike molecules. It is able to recreate experimental structures, decreasing the size of the conformer ensemble needed for good reproduction and the run time required.
Aids the researcher in the selection and preparation of ligands-as well as the desired protein receptor-for a Virtual Screening (VS) procedure. The LigQ web based tool is divided in four semi-independent modules that allow user to determine: 1) the receptor ligand binding pocket, 2) the known ligands for the desired protein and family members, 3) a set of purchasable ligands enriched in potential binders, and 4) 3D structures for selected ligands ready for the VS.
Discovers the X-ray conformation and covers the pharmacophore space. CAESAR is based on a divide-and-conquer approach: recursive decomposition of a molecule into the smallest units followed by recursive buildup of molecular conformations from the smallest units. It can reproduce the receptor-bound X-ray conformations. This approach integrates energy pruning on fine torsion grids instead of the geometry optimization method.
Predicts anticancer potency of an unknown molecule and its GI50 across different cancer cell lines. CancerIN is a web server that consists of three modules for designing, library screening and chemical analogs screening. This web application provides a user-friendly interface with options to draw a chemical compound using Marvin applet. A standalone version of CancerIN is also available and allows users to scan a vast library of molecules for the screening of potential anticancer molecules.
Provides a graphical interface for performing molecular docking simulations. DockingApp is a free platform composed of two main modules: the first one allows docking with manual parameters and the second permits users to perform a virtual screening including a three-dimensional visualization coupled to a result panel. Besides, the software supplies a library containing over 1400 Food and Drug Administration (FDA)-approved drugs and small molecules.
Provides a hybrid ligand/receptor structure-based docking. LigBEnD was developed by incorporating the atomic property field (APF) method into structure-based ensemble docking. This method assumes the following: (1) compounds that are similar to co-crystallized ligands are likely to bind in a similar pose, (2) compounds that are chemically dissimilar to co-crystallized ligands might share similarity in the properties of atoms occupying the same 3D space and (3) compounds belonging to the same chemical class should have consistent, similar poses.
Accounts for receptor flexibility in ligand-receptor docking by iteratively combining rigid receptor docking with protein structure prediction and refinement. Induced Fit generates viable receptor ensembles that can be used in virtual database screens. This tool allows to produce viable receptor structures that, as part of an ensemble with other conformations of the receptor, can produce significantly higher enrichment factors in database screening.
An efficient algorithm that considers both the 3D distribution (shape) and electrostatics of atoms to score and retrieve molecules capable of making similar interactions to those of the supplied query. Cellular and direct binding assays show that UFSRAT successfully identified highly active non-steroid inhibitors with nanomolar activity.
A package which provides a fast and easy way to generate molecular models derived from known inhibitors without the need for information about the receptor. LigMerge algorithm creates novel compounds with structural features similar to those of known ligands. Once generated, LigMerge-derived compounds can be docked into receptor structures to identify likely inhibitors for subsequent synthesis and experimental validation. This tool is useful for those designing custom virtual screening, small-molecule databases when many ligands, potent or otherwise, have been identified experimentally or theoretically via virtual screening.
Classifies molecules as drug-like and nondrug-like molecules. MLViS is based on various machine learning methods, including discriminant, tree-based, kernel-based, ensemble and other algorithms. Besides classification, this application has also the ability to create heat map and dendrogram for visual inspection of the molecules through hierarchical cluster analysis. Moreover, users can connect the PubChem database to download molecular information and to create two-dimensional structures of compounds.
Allows users to manipulate or modify tasks on a protein complex ensemble. toolbx_pdb assists users to study structure-based molecular docking. This tool can setup, monitor and analyze a virtual screening on HPC clusters.
Provides prediction of antibacterial compounds against dihydrodipicolinate synthase (DHDPS). KiDoQ is an approach for prediction of antibacterial compounds that both take quantitative structure–activity relationship (QSAR) and docking strategy into its consideration. The server has employed the molecular docking and ligand based QSAR strategies to predict inhibitory activity value (Ki) of small compounds for DHDPS enzyme.
Provides service to scientific community working in field of drug design against drug resistant Mycobacterium tuberculosis, a causative agent of tuberculosis. MDRIpred allows uses to predict inhibitors against drug-tolerant M.tb H37Rv in different phase like replicate, non-replicative phase.It permits to submit molecule with three options: 1) by drawing structure using JME editor, 2) by pasting molecule in mol/mol2 file format, 3) By file upload.
Permits the preparation of molecules for virtual screening. VSPrep is a comprehensive protocol designed adapted to different types of compounds such as macrocycles and flexible molecules. It is implemented within the pipelining framework KNIME, which consist of instructions (nodes) linked together so that the output of one node becomes the input of the next node. It was designed for datamining, many bioinformatics and chemoinformatics extensions.
Predicts interactions between protein targets and drug-like compounds. PASS Targets is able to predict interactions of drug-like compounds with 2507 protein targets from different organisms based on analysis of structure-activity relationships for 589107 different chemical compounds. This tool was developped using data extracted from the 19th version of the ChEMBL database as a training set and a Bayesian-like method realized in PASS software. PASS (Prediction of Activity Spectra for Substances) provides simultaneous predictions of many types of biological activity based on the structure of organic compounds. It estimates the probable biological activity profiles for compounds under study based on their structural formulae presented in MOLfile or SDfile format.
Identifies inhibitors of a known modulator of G protein-coupled receptor signaling. Screenlamp facilitates: (1) the comparison of molecules in a database for similarity with a known bioactive molecule, (2) the definition of the spatial relationships between chemical groups in a small molecule allowing activation or inhibition of a biological receptor, and (3) the docking of small molecules into a receptor structure to identify the subset of molecules that most favorably interact with the receptor.
Presently, I am working as professor & head of Computational Biology, IIIT-Delhi. Before joining IIT Delhi, I worked as Scientist at Bioinformatics Centre, Institute of Microbial Technology (IMTECH), Chandigarh, India. More information is available from following sites Home Page of Gajendra P. S. Raghava's Group (http://www.imtech.res.in/raghava/) , Computational Resources for Drug Discovery (http://crdd.osdd.net/) , A Customized Operating System for Drug Discovery (http://osddlinux.osdd.net/)and and Gajendra Pal Singh Raghava - Wikipedia (https://en.wikipedia.org/wiki/Gajendra_Pal_Singh_Raghava) .