Useful Molecular Modelling and Drug Design Softwares and Databases
Chemical Structure Database
ZINC: a free database of commercially-available compounds for virtual screening. ZINC contains over 21 million purchasable compounds in ready-to-dock,3D formats. ZINC is provided by the Shoichet Laboratory in the Department ofPharmaceutical Chemistry at the University of California, San Francisco (UCSF). To cite ZINC, please reference: Irwin, Sterling, Mysinger, Bolstad and Coleman, J. Chem. Inf. Model. 2012 DOI: 10.1021/ci3001277.
ChEMBL: It is a database of bioactive drug-like small molecules, it contains 2-D structures, calculated properties (e.g. logP, Molecular Weight, Lipinski Parameters, etc.) and abstracted bioactivities (e.g. binding constants, pharmacology and ADMET data).
ChemSpider: ChemSpider is a free chemical structure database providing fast text and structure search access to over 28 million structures from hundreds of data sources. ChemSpider SyntheticPages, CS|SP, extends this model to cover reactions, providing quick publication, peer review and semantic enhancement of repeatable reactions. Maintained by: Royal Society of Chemistry
Drug Bank: The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information. The database contains 6712 drug entries including 1448 FDAapproved small molecule drugs, 131 FDA-approved biotech (protein/peptide) drugs, 86 nutraceuticals and 5079 experimental drugs and many more. Supported By: Genome Alberta & Genome Canada. This project is also supported in part by GenomeQuest, Inc.
PubChem: Database of molecules with their properties,bioassay result,3D structuresand with many more informations. Copyright: National Center for BiotechnologyInformation (NCBI)
Approved Drugs: The Approved Drugs app contains over a thousand chemicalstructures and names of small molecule drugs approved by the US Food & DrugAdministration (FDA). Structures and names can be browsed in a list, searched byname, filtered by structural features, and ranked by similarity to a user-drawnstructure. Developed by: Molecular Materials Informatics, Inc. Check iTUNES
e-Drug3D: Currently 1595 molecular structures with a molecular weight < 2000have been registered. Copyright: Institut de Pharmacologie Moléculaire et Cellulaire
KEGG DRUG: comprehensive drug information resource for approved drugs inJapan, USA, and Europe unified based on the chemical structures and/or the chemicalcomponents, and associated with target, metabolizing enzyme, and other molecularinteraction network information. Developed by: Kyoto Encyclopedia of Genes andGenomes.
eMolecules: Free chemical structure search engine with millions of public domainstructures from vendors worldwide. Copyright: eMolecules, Inc.
JChem for Excel : It provides structure handling and visualizing capabilities within aMicrosoft Excel® environment. Structures are fully supported within spreadsheetsand can be viewed, edited, searched, resized, ordered, managed. Implementation isrobust with fast loading/scrolling of many hundreds of structure rows and copy-pastethroughout the Microsoft Office® suite. Copyright ChemAxon Ltd.
Bingo : Bingo is a RDBMS data cartridge that provides the industry’s nextgeneration,fast, scalable, and efficient storage and searching solution for chemicalinformation. Copyright GGA Software Services LLC.
Protein Data Bank or Database of Ligand and Protein Complexes :
RCSB-PDB: Most prominent database of structures of proteins, nucleic acids, andcomplex of ligand-protein etc. Copyright RCSB Protein Data Bank
Binding MOAD : a subset of the Protein Data Bank (PDB), containing every highquality example of ligand-protein binding. Hence, we call it the Mother of AllDatabases (MOAD). Binding MOAD’s goal is to be the largest collection of wellresolved protein crystal structures with clearly identified biologically relevant ligandsannotated with experimentally determined binding data extracted from literature.Reference: L Hu, ML Benson, RD Smith, MG Lerner, HA Carlson. Binding MOAD (Mother Of All Databases). Proteins 2005, 60, 333-40
PDBbind Database: is designed to provide a collection of experimentally measuredbinding affinity data (Kd, Ki, and IC50) exclusively for the protein-ligand complexesavailable in the Protein Data Bank (PDB). References: Wang, R.; Fang, X.; Lu, Y.;Yang, C.-Y.; Wang, S. “The PDBbind Database: Methodologies and updates”, J.Med. Chem., 2005; 48(12); 4111-4119. Wang, R.; Fang, X.; Lu, Y.; Wang, S. “ThePDBbind Database: Collection of Binding Affinities for Protein-Ligand Complexeswith Known Three-Dimensional Structures”, J. Med. Chem., 2004; 47(12); 2977- 2980.
SCORPIO: It is a FREE online repository of protein-ligand complexes which havebeen structurally resolved and thermodynamically characterized.
BindingDB: It is a public, web-accessible database of measured binding affinities,focusing chiefly on the interactions of protein considered to be drug-targets withsmall, drug-like molecules. BindingDB contains 910,836 binding data, for 6,263protein targets and 378,980 small molecules.
AffinDB: Affinity database of Protein-Ligand Complexes. Copyright Peter Block,Christoph Sotriffer, Gerhard Klebe 2002-2013
LigandProtein Database: A collection of ligand-protein complexes, with 3D structuresand experimental binding free energies. Created by: Professor Charles L. Brooks, IIIDepartment of Chemistry, Biophysics Program 930 N. University Ave; University ofMichigan
Drug Target Database:
TTD. (Therapeutic Target Database): A database to provide information about theknown and explored therapeutic protein and nucleic acid targets, the targeted disease,pathway information and the corresponding drugs directed at each of these targets.Also included in this database are links to relevant databases containing informationabout target function, sequence, 3D structure, ligand binding properties, enzymenomenclature and drug structure, therapeutic class, clinical development status.Created by: Dr. Chen Yuzong Deputy Director of Center for Computational Scienceand Engineering; Professor in Department of Pharmacy National University ofSingapore, SingaporeMolecule Pathway Database
SMPDB (The Small Molecule Pathway Database): It is an interactive, visual database containing more than 350 small molecule pathways found in humans. More than 2/3of these pathways (>280) are not found in any other pathway database. SMPDB isdesigned specifically to support pathway elucidation and pathway discovery inmetabolomics, transcriptomics, proteomics and systems biology. This project issupported by Genome Alberta & Genome Canada.
Chemical Structure Drawing Programmes
ChemDraw. Chemical structure drawing software developed by CambridgeSoft.Available for Windows and Mac.
MarvinSketch. JAVA based chemical editor for drawing chemical structures,queries and reactions,NMR prediction and much more developed byChemAxon.Avaiable for WINDOWS and MAC.
ACD/ChemSketch. ChemSketch is a chemical structure drawing program developedby ACD/Labs. Among other features, ChemSketch has the ability to:Draw and view structures in 2D, or render in 3D to view from any angleDraw reactions and reaction schemes, and calculate reactant quantities Generate structures from InChI and SMILES stringsGenerate IUPAC systematic names for molecules of up to 50 atoms and 3 ringstructuresPredict logP for individual structuresSearch for structures in the built-in dictionary of over 165,000 systematic, trivial, andtrade names. Users can download a freeware version of the software on the ACD/Labs website.The full version of the software is also available for purchase.
JChem for Excel. It provides structure handling and visualizing capabilities within aMicrosoft Excel® environment. Structures are fully supported within spreadsheetsand can be viewed, edited, searched, resized, ordered, managed. Implementation isrobust with fast loading/scrolling of many hundreds of structure rows and copy-pastethroughout the Microsoft Office® suite. Copyright ChemAxon Ltd.
Accelrys Draw. It enables scientists to draw and edit complex molecules, chemicalreactions and biological sequences with ease, facilitating the collaborative searching,viewing, communicating, and archiving of scientific information. Copyright: Accelrys
BKchem: It is a free software chemical drawing program. It was conceived andwritten by Beda Kosata and is currently maintained by Reinis Danne. BKChem is written in Python, an interpreted and very nice programming language.This implies some of the program features:platform independence – BKChem shouldrun on any platform that Python does.*performance – as Python is interpretedlanguage you should not expect the performance of a native code compiledapplication (in present days a very cheap tradeoff for platform independence).However BKChem should be pretty usable on all modern systems.BKChem isdeveloped on GNU/Linux. It was however successfully used under WinXPand MacOS X.
JME Molecular Editor: It is a Java applet which allows to draw / edit molecules andreactions (including generation of substructure queries) and to depict moleculesdirectly within an HTML page. Editor can generate Dayligh SMILES or MDL molfile of created structures. The applet has been developed by Peter Ertl at ComeniusUniversity Bratislava and later enhanced at Ciba-Geigy Basel.
Marvin molecule editor and viewer. Java based chemical editor uses MARVINapplet. Developed by: ChemAxon.
Molinspiration WebME Molecule Editor. It allows allows creation and editing ofmolecules in browsers without Java support and without any plugins. The editor isbased on a Web2.0 Ajax technology. WebME allows therefore web-based structureinput also in institutions where Java applets are not allowed and offers completeplatform compatibility. The actual molecule processing in WebME is based onreliable JMEPro editing engine running on a server.
Three Dimensional Viewing (3-D Viewing)
UCSF Chimera : is a highly extensible program for interactive visualization andanalysis of molecular structures and related data, including density maps,supramolecular assemblies, sequence alignments, docking results, trajectories, andconformational ensembles. High-quality images and animations can be generated.Chimera is developed by the Resource for Biocomputing, Visualization, andInformatics, funded by the National Institutes of Health (NIGMS P41-GM103311)
PYMOL: is a user-sponsored molecular visualization system on an opensourcefoundation. Please support development of this open, effective, and affordablesoftware by purchasing an incentive copy, which is pre-built and comes withmaintenance and support. Distributed by DeLano Scientific LLC.
SWISS PDB VIEWER: Swiss-PdbViewer (aka DeepView) is an application thatprovides a user friendly interface allowing to analyze several proteins at the sametime. The proteins can be superimposed in order to deduce structural alignments andcompare their active sites or any other relevant parts. Amino acid mutations, H-bonds,angles and distances between atoms are easy to obtain thanks to the intuitive graphicand menu interface. Copyright Swiss Institute of Bioinformatics
Autodock/Vina Plug-In for Pymol: It contains a bunch of new features such as • Defining binding sites and export to Autodock and VINA input files • Doing receptor and ligand preparation automatically • Starting docking runs with Autodock or VINA from within the plugin • Viewing grid maps generated by autogrid in PyMOL • Handling multiple ligands and set up virtual screening etc. Copyright Daniel Seeliger
Computer-Aided Drug-Design Platform using PyMOL: PyMOL plugins forprotein preparation (AMBER package and Reduce), molecular mechanicsapplications (AMBER package), and docking and scoring (AutoDock Vina andSLIDE). Copyright Purdue University
Jmol: an open-source Java viewer for chemical structures in 3D
ICM-Browser: Molecule Visualization, Fully Interactive 3D Slides in PowerPointand Web, Publication Quality Images, Display Ligand Binding Pocket Surfaces,Hydrogen Bond Display, Measure Distances and Angles and much more. CopyrightMolsoft LLC
YASARA: It is a molecular-graphics, -modeling and -simulation program forWindows, Linux and Mac OS X. Copyright Elmar Krieger.
RasMol: It is a program for molecular graphics visualisation originally developed byRoger Sayle
Molegro Molecular Viewer: Molegro Molecular Viewer is a free cross-platformapplication for the visualization of molecules and Molegro Virtual Dockerresults.Copyright CLC bio. A result of science.
Programmes for File Format Conversion
Open Babel: is a chemical toolbox designed to speak the many languages of chemicaldata. It’s an open, collaborative project allowing anyone to search, convert, analyze,or store data from molecular modeling, chemistry, solid-state materials, biochemistry,or related areas.Citation J. Cheminf. 2011, 3:33
OSRA: Optical Structure Recognition Application: is a utility designed to convertgraphical representations of chemical structures, as they appear in journal articles,patent documents, textbooks, trade magazines etc., into SMILES (SimplifiedMolecular Input Line Entry Specification – see http://en.wikipedia.org/wiki/SMILES)or SD files – a computer recognizable molecular structure format. OSRA can read adocument in any of the over 90 graphical formats parseable by ImageMagick –including GIF, JPEG, PNG, TIFF, PDF, PS etc., and generate the SMILES or SDFrepresentation of the molecular structure images encountered within that document.
Mol2Mol: recognizes, reads and writes about 50 different file formats andsubformats. It contains a simple graphic display module to inspect the currentlyloaded molecule. It possesses some chemical intelligence for recognizing detailedatom types, hybridization and chemical environments, which is necessary forconverting simpler formats (like X-ray crystallographic files) to more advanced ones,or when hydrogen atoms are automatically to be added to the heavy atoms.Problematic files can be corrected within Mol2mol or as ASCII files by callingdirectly your favourite text editor.
Visualisation and Analysis of Protein-Ligand Interaction
Pose View: automatically generates high-quality 2D structure-diagrams of protein ligandcomplexes provided as 3D-input. Such input may come directly from crystalstructures or be computed for example by a docking program.
LigPlot: Generates 2-D ligand interaction maps.
Maestro Ligand Interaction: 2-D ligand interaction map using Maestro’s freegraphical user interface.
Autodock. It is a suite of automated docking tools. It is designed to predict howsmall molecules, such as substrates or drug candidates, bind to a receptor of known3D structure. Maintained by the Molecular Graphics Laboratory, The ScrippsResearch Institute, la Jolla.
Autodock VINA. It is a new open-source program for drug discovery, moleculardocking and virtual screening, offering multi-core capability, high performance andenhanced accuracy and ease of use. It has been designed and implemented by Dr.Oleg Trott in the Molecular Graphics Lab at The Scripps Research Institute.
DOCK. the DOCK algorithm addressed rigid body docking using a geometricmatching algorithm to superimpose the ligand onto a negative image of the bindingpocket. Important features that improved the algorithm’s ability to find the lowest energybinding mode, including force-field based scoring, on-the-fly optimization, animproved matching algorithm for rigid body docking and an algorithm for flexibleligand docking, have been added over the years. Copyright Soichet group at theUCSF.
GOLD. Genetic Algorithm based docking program. GOLD enables you to makeconfident binding mode predictions, and achieve high database enrichments. GOLDreliably identifies the correct binding mode for a large range of test set cases, and hasbeen shown to perform favourably against other docking tools in numerousindependent studies. Copyright University of Sheffield, GlaxoSmithKline plc andCCDC.
Glide. It offers the full spectrum of speed and accuracy from high-throughput virtualscreening of millions of compounds to extremely accurate binding mode predictions,providing consistently high enrichment at every level. Copyright Schrödinger.
GlamDock. It is based on a Monte-Carlo with minimization (basin hopping) search ina hybrid interaction matching / internal coordinate search space. GlamDock is highlyefficient, taking from 5 seconds (fast virtual screening settings) to ~20 seconds (highquality docking settings) on average on standard 2.8GHz Intel Xeon CPUs.
GEMDOCK. Generic Evolutionary Method for molecular DOCKing GEMDOCK isa program for computing a ligand conformation and orientation relative to the activesite of target protein. The tool was developed by Jinn-Moon Yang, a profesor of theInstitute of Bioinformatics, National Chiao Tung University.
HomDock. is a combination of the ligand based GMA molecular alignment tool andGlamDock.
ICM. ICM-Docking and chemistry module provides access to the chemicalinformation and provides a unique set of tools for accurate individual ligand-proteindocking, peptide-protein docking, and protein-protein docking, including interactive graphics tools. With the ICM-Dock module, you can do rapid and accurate dockingsimulations. Copyright MolSoft.
FlexX, Flex-Ensemble (FlexE). Incremental build based docking program. Flexibleligand. Protein flexibility through ensemble of protein structure. CopyrightBioSolveIT.
FITTED (Flexibility Induced Through Targeted Evolutionary Description). Itaims at improving the accuracy of existing molecule docking software program. Ituses a more accurate protein models and is based on a pharmacophore-orienteddocking method combined with a genetic algorithm based docking approach. Thelater takes advantage of more than one structure to dock compounds in virtuallyflexible proteins.
VLifeDock. Uses three docking approaches e.g. Grid based docking, GA docking andVLife’s own GRIP docking program. WINDOWS, LINUX version is availableCopyright VLife.
Molegro Virtual Docker. It is an integrated platform for predicting protein – ligandinteractions. Molegro Virtual Docker handles all aspects of the docking process frompreparation of the molecules to determination of the potential binding sites of thetarget protein, and prediction of the binding modes of the ligands.
OEDocking OEDocking is a suite of well-validated molecular docking tools and theirassociated workflows. Each tool is specifically designed to address its own uniqueapplication to the docking problem.OEDocking features POSIT for informed poseprediction as well as FRED andHYBRID as complementary tools for virtualscreening.
Online Docking Programmes
1-Click Docking: Upload your molecule choose a target from the list and click onDOCK. Copyright Mcule Inc.
Swiss Dock: It a web service to predict the molecular interactions that may occurbetween a target protein and a small molecule.Copyright Swiss Institute ofBioinformatics.
ParDOCK: Automated server for rigid docking. Copyright Prof B. Jayaram & Coworkers.DNA Ligand Docking It is an all-atom energy based Monte Carlo DNA liganddocking, implemented in a fully automated, parallel processing mode which predictsthe binding mode of the ligand in the minor groove of DNA. The input is a DNAsequence and drug PDB file. The output will a docked structure along with the bindingaffinity of the docked structures. Copyright Swiss Institute of Bioinformatics
DockingServer It offers a web-based, easy to use interface that handles all aspectsof molecular docking from ligand and protein set-up.Copyright Virtua Drug
FlexPepDock is a high-resolution peptide docking (refinement) protocol,implemented within the Rosetta framework. The input for this server is a PDB file ofa complex between a protein receptor (first chain) and an estimated conformation fora peptide (second chain). FlexPepDock was shown to be able to accurately refine thepeptide structure starting from up to 5.5A RMSD of the native conformation,allowing full flexibility to the peptide and side-chain flexibility to the receptor.
PatchDock is an algorithm for molecular docking. The input is two molecules of anytype: proteins, DNA, peptides, drugs. The output is a list of potential complexessorted by shape complementarity criteria.
DOCK Blaster, a public access service for structure-based ligand discovery.
INVDOCK, has been developed for computer-automated identification of potentialprotein and nucleic acid (RNA or DNA) targets of a small molecule (such as a drug,newly designed drug candidate, natural product or other chemical compound).
Softwares for Molecular Dynamics
1. AMBER: AMBER is a biomolecular package which deals with mainly two thingsa. a set of force field b. a biomolecular simulation package with MM and QM/MMsimulation capability.
2. Desmond: Desmond is a high performance molecular dynamics package developedby D.E. Shaw research. Its source code is is available without cost for academic use.
3. Gromacs: Free and open source molecular dynamics package capable of tosimulate biomolecular systems e.g. protein lipid etc.
4. COSMOS: Hybrid QM/MM molecular dynamics, NMR structure calculations etc.
5. CHARMM: Widely used force fields and molecular dynamics simulation packagedeveloped by Martin Karplus and his group at Harvard.
6. LAMMPS: Large-scale Atomic/Molecular Massively Parallel Simulator, amolecular dynamics simulation package which uses MPI for parallel simulation.
7. Materials Studio: Commercial package to simulate and modelling materials.
8. SCIGRESS: Commercial molecular dynamics package for performing MM, DFT,semiemperical methods, linear scaling SCF, conformational analysis etc.
9. TeraChem: High performance ab-initio molecular dynamics and DFT softwarepackage with GPU acceleration.
10. NAMD: Its parallel efficiency molecular dynamics simulation package often usedto simulate large biomolecular systems.
TOOLS FOR TARGET PREDICTION
MolScore-Antivirals is an expert system, which can detect molecules with antiviralactivity. The expert system analyses the probability of a compound to become anantiviral drug and is defined as a value between 0 and 1.Copyright PharmaInformaticBoomgaarden
MolScore-Antibiotics discriminates between antibiotics and non-antibiotics. TheMolScore-Antibiotics of a compound measures the probability of having antibioticactivity and is defined as a value between 0 and 1. Copyright PharmaInformaticBoomgaarden
TarFisDock : a web server for identifying drug targets with docking approach.
ReverseScreen3D is a reverse virtual screening tool that searches against abiologically-relevant and automatically-updated subset of ligands extracted fromthe RCSB Protein Data Bank in order to identify potential target proteins that arelikely to bind a given compound.
BIOLOGICAL ACTIVITY PREDICTION
PASS (Prediction of Activity Spectra for Substances): It estimates the probablebiological activity profiles for compounds under study based on their structuralformulae presented in MOLfile or SDfile format. General list of predictable biologicalactivities consists of over 4,000 terms including pharmacotherapeutic effects (e.g.,antiarrhythmic), biochemical mechanisms (e.g., cyclooxygenase 1 inhibitor), toxicity(e.g., carcinogenic), metabolism (e.g., CYP3A4 inhibition), gene expressionregulation (e.g., VEGF expression inhibition), transporter-related activities (e.g., Pglycoproteinsubstrate). PASS prediction is based on the knowledge base aboutstructure-activity relationships for more than 260,000 compounds with knownbiological activities. Average accuracy of prediction estimated in leave-one-out crossvalidationprocedure for the whole PASS training set is about 95%.
MOST USER FRIENDLY ADME, TOXICITY PREDICTION TOOL
preADMET : Web based application for prediction of different ADME and toxicityparameters. Works with Internet Explorer and Netscape browser. PC version is alsoavailable.
SYBYL-X : It has the capabilities for small molecule modeling and simulation,macromolecular modeling and simulation, cheminformatics, lead identification, andlead optimization, all wrapped up in an easy to use, cost-effective interface. You canperform 3D-QSAR, Ligand Based Virtual Screening,Cheminformatics,Docking withSYBYL. Copyright Tripos,L.P
It is hard to make a rich list of all tools with proper description. You can always suggest improvements in order to to make this list a complete one. Direct your queries at firstname.lastname@example.org