PPI hotspots, Interface residues, PPI drug-like modulators

 

  • Protein WISDOM - The framework is divided into two stages: a sequence selection stage and a validation stage. The sequence selection stage designs novel protein and peptide sequences based upon a rigid or flexible design template uploaded by the user. Once sequence are generated, they can be validated by either fold specificity or approximate binding affinity. Fold specificity is a measure of how well the designed sequence adopts the template fold while approximate binding affinity is a measure of how well the designed sequence binds to a given protein target - online
  • BindUP - Non-homology-based prediction of DNA and RNA binding proteins - online
  • IBIS - Inferred Biomolecular Interaction Server - online
  • PinaColada - Design of protein-protein interaction (PPI) inhibitors is a major challenge in Structural Bioinformatics. Peptides are natural candidates for inhibition of protein-protein complexes. PinaColada, a novel computational method for the design of peptide inhibitors for protein-protein interactions (2016) - online
  • MoRFchibi - Tools for the identification of MoRFs (short segments within longer disordered protein regions that bind to globular protein domains in a process known as disorder-to-order transition) in protein sequences (2016) - online
  • iFraG - A protein–protein interface prediction server based on sequence fragments (2016) - online
  • HotSpot - HotSpot Wizard 2.0 is a web server for automated identification of hot spots and design of smart libraries for engineering proteins’ stability, catalytic activity, substrate specificity and enantioselectivity. The server integrates sequence, structural and evolutionary information obtained from 3 databases and 20 computational tools (2016) - online
  • Mechismo - Predicting the mechanistic impact of mutations and modifications on molecular interactions (protein-protein, PPi) - online
  • MutaBind - Estimates and interprets the effects of sequence variants on protein–protein interactions - online
  • iPPBS-Opt - A Sequence-Based Ensemble Classifier for Identifying Protein-Protein Binding Sites by Optimizing Imbalanced Training Datasets (2016) - online
  • PrePPItar - With the booming of interactome studies, a lot of interactions can be measured in a high throughput way and large scale datasets are available. It is becoming apparent that many different types of interactions can be potential drug targets. Compared with inhibition of a single protein, inhibition of protein–protein interaction (PPI) is promising to improve the specificity with fewer adverse side-effects. Also it greatly broadens the drug target search space, which makes the drug target discovery difficult. Machine learning method to predict PPI targets in a genomic-wide scale - online
  • MolStructPred - Solvent Accessible Surface Area-Based Hot-Spot Detection Methods for Protein–Protein and Protein–Nucleic Acid Interfaces (2015). SASA-HS-PNA, SASA-HS-PP - online
  • AlphaSpace - Fragment-Centric Topographical Mapping to Target Protein-Protein Interaction Interfaces (2015) - standalone
  • PSIVER - PSIVER is a server for the prediction of protein-protein interaction sites in protein sequences - online
  • I-COMS - Interprotein-COrrelated Mutations Server. Allows to estimate covariation between residues of different proteins by four different covariation methods. Results might be used to prioritize protein positions in a mutation analysis based on their inter and intra (if part of a complex) coevolutionary role. It might also provide a guide for docking experiments and to gain insights into protein–protein interaction when a structure of the complex is not available - online
  • jsPISA - Analysis of macromolecular interfaces and identification of biological assemblies (complexes) from macromolecular crystal structures (2015) - online
  • CompASM - Computational Alanine Scanning Mutagenesis presents here as a very intuitive plug-in for two widely distributed software (AMBER and Visual Molecular Dynamics – VMD) that allows the user to perform a full Alanine Scanning Mutagenesis (ASM) procedure, requiring only very little user effort. It is composed of two main packages: the Core and Graphical User Interface (GUI) - standalone
  • Profppikernel - Evolutionary profiles improve protein–protein interaction prediction from sequence - standalone
  • Ccharppi - Computational Characterisation of Protein-Protein Interactions - online
  • Structure-PPi - A module for the annotation of cancer-related single-nucleotide variants at protein-protein interfaces. The Structure-PPi system for the comprehensive analysis of coding SNVs based on 3D protein structures of protein complexes. The 3D repository used, Interactome3D, includes experimental and modeled structures for proteins and protein-protein complexes. Structure-PPi annotates SNVs with features extracted from UniProt, InterPro, APPRIS, dbNSFP, and COSMIC databases - standalone
  • PPI tool - 3D Complex is a hierarchical classification of protein complexes that describes similarities in structure, sequence, as well as topology of contacts of the constituent proteins - online
  • Mutation tool - Inferring the microscopic surface energy of protein-protein interfaces from mutation data (2015) - online
  • CONSRANK - A server for the analysis, comparison and ranking of docking models based on inter-residue contacts - Online
  • CRF - CRF-based models of protein surfaces improve protein-protein interaction site predictions - Online
  • eFindSitePPI - The tool detects protein binding sites and residues using meta-threading. It also predicts interfacial geometry and specific interactions stabilizing protein-protein complexes, such as hydrogen bonds, salt bridges, aromatic and hydrophobic interactions - Online and standalone
  • mcsm-ppi - Protein-Protein Affinity Change Upon Mutation - Online
  • iAlign - Structural comparison of protein-protein interfaces - standalone
  • CCharPPI - CCharPPI calculates up to 108 parameters, including models of electrostatics, desolvation and hydrogen bonding, as well as interface packing and complementarity scores, empirical potentials at various resolutions, docking potentials and composite scoring functions - online
  • PPA_Pred - Protein-protein binding affinity prediction from amino acid sequence - online
  • LoopFinder for PPI cmpd design - A web-based interface for LoopFinder is currently under construction. In the meantime, LoopFinder is freely available for use. Requests for binary files or code can be sent to This email address is being protected from spambots. You need JavaScript enabled to view it. (Gavenonis et al, Nat Chem Biol. 2014) - standalone for now
  • PPI-Server - The classification of protein-protein interactions into permanent, transient and crystal artifacts is still an unsolved problem. This server investigates this question - online
  • EPPIC - Evolutionary Protein Protein Interface Classifier (Duarte et al, BMC Bioinformatics, 2012) aims at distinguishing biologically relevant interfaces from crystal contacts in protein crystal structures. The approach was also successfully used in Dr. Capitani's lab to investigate oligomerization interfaces in transmembrane proteins - online
  • COCOMAPS - bioCOmplexes COntact MAPS is a web application to easily and effectively analyse and visualize the interface in biological complexes (such as protein-protein, protein-DNA and protein-RNA complexes), by making use of intermolecular contact maps - online
  • PredHS - A web server for predicting protein–protein interaction hot spots by using structural neighborhood properties - online
  • CAD-score - The CAD-score web server: contact area-based comparison of structures and interfaces of proteins, nucleic acids and their complexes - online
  • PredictProtein - Open resource for online prediction of protein structural and functional features. A meta-service for sequence analysis that has been predicting structural and functional features of proteins since 1992. Queried with a protein sequence it returns: multiple sequence alignments, predicted aspects of structure (secondary structure, solvent accessibility, transmembrane helices (TMSEG) and strands, coiled-coil regions, disulfide bonds and disordered regions) and function. The service incorporates analysis methods for the identification of functional regions (ConSurf), homology-based inference of Gene Ontology terms (metastudent), comprehensive subcellular localization prediction (LocTree3), protein–protein binding sites (ISIS2), protein–polynucleotide binding sites (SomeNA) and predictions of the effect of SNPs on protein function (SNAP2) - online
  • DoReMi - Context-based prioritization of linear motif matches - online
  • PSIPRED and HSPred - Hotspot predictions - online
  • Rosetta - Rosettacommons, protocols to design oxopiperazine helix mimetics and other peptides for PPI - online
  • AquaProt - AquaProt analyses protein-protein binding interface, defines inter-residue interaction map within the interface and extracts related water molecules - online
  • VASCo - VASCo is a program pipeline including a visualization tool to calculate and visualize annotated surfaces with special emphasis on surface contact regions and protein-protein interactions - standalone
  • hotspot predictors - Accurate prediction of hot spot residues through physicochemical characteristics of amino acid sequences - standalone
  • SEQMOL - SEQMOL is a PDB structure analysis suite. It can be used to align multiple protein and DNA sequences, compute evolutionary attributes of multiple sequence alignments (such as sequence conservation, hydrophobicity conservation, conformational flexibility conservation, physical covariation, protein-protein interface (has the ODA tool and Conservation of protein-protein interaction propensity), Nucleic acid desolvation analysis, protein-RNA interface and protein-DNA interface propensity (Predicting protein-RNA binding sites via residue interface propensity conservation with subsequent patch energy calculation), and conservations thereof) and to map these features onto PDB files. Many of the features do not use multiple sequence alignment and directly analyze PDB coordinates to yield insights that could often be valuable. Binding constants prediction module for PDB complexes and crystal contacts based on a de-novo built algorithm with sound Kd accuracy Kd predictions in SEQMOL are user-friendly and usually fast (seconds-minutes for average-sized complexes on a local CPU). A PDB file is DragDropped onto the application. Kd along with a comprehensive interface analysis is produced in the output. For multiple-PDB jobs, such as scoring of decoys from docking programs, batch PDB processing is done automatically if more than one PDB was DragDropped - standalone
  • HotPatch - HotPatch finds unusual patches on the surface of proteins, and computes just how unusual they are (patch rareness), and how likely each patch is to be of functional importance - online
  • ET-viewer - ET viewer: an application for predicting and visualizing functional sites in protein structures. The Evolutionary Trace Viewer (ETV) provides a one-stop environment in which to run, visualize and interpret Evolutionary Trace (ET) predictions of functional sites in protein structures - online
  • DoBi - Find binding sites and can be used for docking - standalone
  • TreeDet - Predicting Functional Residues in Protein Sequence Alignments. (help to predict interface residues, co-evolution) - standalone
  • Patch Finder Plus (PFplus) - A web server for extracting and displaying positive electrostatic patches on protein surfaces - online
  • Crescendo - Crescendo is a program for identifying functional sites in proteins. It distinguishes structural and functional restraints in evolution in order to identify interaction sites - online
  • HADDOCK2P2I - A robust biophysical model for predicting the binding affinity of protein-protein interaction inhibitors - online
  • surface triplet propensities or STP - Identification of protein binding surfaces using surface triplet propensities. The method described here does not explicitly look for cavities but uses small surface patches consisting of triplets of adjacent surface atomic groups that can be touched simultaneously by a probe sphere representing a solvent molecule - online
  • FragVLib - FragVLib a free database mining software for generating Fragment-based Virtual Library using pocket similarity search of ligand-receptor complexes. A free software which is developed as a tool for performing similarity search across database(s) of ligand-receptor complexes for identifying binding pockets which are similar to that of a target receptor - standalone
  • PAIRpred - Partner-specific prediction of interacting residues from sequence and structure - python scripts
  • MMDB and VAST+ - Tracking structural similarities between macromolecular complexes - online
  • iPred - Protein-Protein Interface and Hot-Spot Prediction - online
  • MetaPPI - A meta approach to predict protein-protein interaction binding site, combines PPI-PRED, PPISP, PINUP, Promate, SPPIDER - online
  • PRICE - Energetics of PPI interfaces - conservations - online
  • RosettaBackrub - Flexible backbone protein structure modeling and design server. Can be used for Point mutation, Backbone ensemble (creates near-native structural ensembles), Sequence tolerance (predicts sequences tolerated for proteins and protein-protein interfaces using flexible backbone design methods. Example applications are the generation of sequence libraries for experimental screening and prediction of protein or peptide interaction specificity) - online
  • PATRIC - PATRIC, the bacterial bioinformatics database and analysis resource - online
  • EleKit - EleKit allows to measure the similarity of electrostatic potentials between a docked small molecule and a known ligand protein for the same receptor. EleKit is intended to facilitate the design of SMPPIIs (Small Molecule Protein-Protein Interaction Inhibitors) - standalone
  • HOMOLOBIND - HOMOLOBIND identifies residues in protein sequences with significant similarity to structurally characterized binding sites - online
  • PPIcons - PPIcons: identification of protein-protein interaction sites in selected organisms - standalone
  • SPPIDER - SPPIDER prediction of PPI binding sites (use 3D structure or sequence) - online
  • Dsppi - Dsppi : Drugscore-PPI is a knowledge-based scoring function for computational alanine-scanning in protein-protein interfaces - online
  • Score-MI - An information-theoretic classification of amino acids for the assessment of interfaces in protein-protein docking. The reduced alphabets derived from the present work were converted into a scoring function for the evaluation of docking solutions, which is available for public use via the web service score-MI - online scoring
  • PPIevo - PPIevo: Protein-protein interaction prediction from PSSM based evolutionary information - standalone
  • PPI Affinity prediction - Protein-protein binding affinity prediction on a diverse set of structures - online
  • PPI prediction - PPI Prediction Server classifies a protein-protein complex concerning its interaction type into permanent, transient or crystal artifact. The discrimination is performed using two characteristics of the protein-protein complex, the hydrophobicity of the interface and the quotient of interface area ratios - online
  • Link - BeAtMuSiC : prediction of changes in protein-protein binding affinity on mutations - online
  • dPred - A program to calculate the desolvation penalties of small probes in cavities to identify possible binding sites of small ligands - standalone
  • Proface - Analysis of protein-protein interface online - online
  • PI2PE - Protein interface-interior prediction engine - online
  • 3D-Surfer - Offers web-based tools for rapid protein surface analysis and comparison. The server integrates various methods to assist in the high throughput screening and visualization of protein surface comparisons - online
  • InterProSurf - Protein-Protein Interaction Server online - online
  • Intervor - Investigating MacroMolecular Interfaces - online
  • PDBePISA - Protein Interfaces, Surfaces and Assemblies - online
  • BIPS - BIANA Interolog Prediction Server. A tool for protein-protein interaction inference - online
  • I2I-SiteEngine - Structural and Physico-Chemical Alignment of Protein-Protein Interfaces - online
  • DiMoVo - DIscriminate between Multimers and MOnomers by VOronoi tessellation - online
  • Dr PIAS - Druggable Protein-protein Interaction Assessment System - Protein-protein interaction PPI
  • JCB - Numerous information and Links: protein interaction network and databases of complexes can be found at the JCB Protein-Protein Interaction Website - Links and tools for macromolecular interactions
  • MolSurfer - A macromolecular interface navigator - Interface analysis standalone and online
  • Link - Biomolecular modelling group: several tools for PPIs - online and standalone
  • AquaSAXS - A web server for computation and fitting of SAXS profiles with non-uniformally hydrated atomic models - online
  • Drug-SNPing - An integrated drug-based, protein interaction-based tagSNP-based pharmacogenomics platform for SNP genotyping All drug-based and protein-protein interaction-based SNP genotyping information are provided with PCR-RFLP (PCR-restriction enzyme length polymorphism) and TaqMan probes - online
  • PS-HomPPI - A sequence-based partner-specific protein-protein interface residue prediction server - online
  • NPS-HomPPI - A sequence-based non-partner-specific protein-protein interface residue prediction server - online
  • PBSword - A web server designed for efficient and accurate comparisons and searches of geometrically similar protein-protein binding sites from a large-scale database - online
  • SynSysNet - Based on an expert-curated list of 1.000 human genes, specific to the synapse. Information on resulting proteins, their 3D structure, binding small molecules Protein-Protein-Interactions (PPIs) and Compound-Protein-Interactions are integrated - online
  • DOMINO - An open-access database comprising more than 3900 annotated experiments describing interactions mediated by protein-interaction domains - database
  • SNAPPI - Structures, iNterfaces and Alignments for Protein-Protein Interactions SNAPPI-DB is a database of domain-domain interactions SNAPPI-Predict is a protein-protein interaction prediction program which is currently in development SNAPPI-View is the web interface to SNAPPI-DB and SNAPPI-Predict - online
  • InterEvScore - A novel coarse-grained interface scoring function using a multi-body statistical potential coupled to evolution - standalone
  • PPISURV - A novel bioinformatics tool for uncovering the hidden role of specific genes in cancer survival outcome online PPI - online
  • NETAL - A new graph-based method for global alignment of protein-protein interaction networks - standalone Binaries supported linux
  • PredUs - Prediction of Protein Interfaces Using Structural Alignment - online
  • KBDOCK - 3D database system that defines and spatially clusters protein binding sites for knowledge-based protein docking. KBDOCK integrates protein domain-domain interaction information from 3DID and sequence alignments from PFAM together with structural information from the PDB in order to analyse the spatial arrangements of DDIs by Pfam family, and to propose structural templates for protein docking - Database PPI
  • iLoops - Uses protein structural features (loops and domains) of interacting and non-interacting protein pairs to determine whether any pair of proteins interacts or not - online
  • CSPred-PPI - Combines a compressed sensing (CS) algorithm and support vector machines to predict Saccharomyces cerevisiae PPIs from primary sequence - online
  • CD - A sequence-based co-evolutionary divergence (CD) method for PPIs prediction in the human proteome - standalone
  • ISMBLab_PPI - A machine-learning algorithm that predicts PPIs sites based on the distribution of physicochemical complementarity features of non-covalent interacting atoms in protein surfaces - online
  • iWRAP - Predicts PPIs and their interfaces based on a protein interface threading approach - online
  • P.R.I.S.M. - A web-server that can be used to explore protein interfaces and predict protein-protein interactions (PRISM). The server is now server is out of service and not up-to-date - online
  • HotRegion - HotRegion: a database of predicted hot spot clusters - database
  • CMA - Contact Map Analysis (CMA) webserver. This program allows to analyse contacts between two chains or within one chain in a given PDB file - online
  • PCRPi-W - Presaging Critical Residues in Protein interfaces-Web Server (PCRPi-W): A Web Server to Chart Hot Spots in Protein Interfaces - online
  • BioCreAtIvE - Community-wide assessment of text mining methods - .
  • SGI - Second generation structural genomics initiatives focus on protein complexes - .
  • Trypano-PPI - A web server for prediction of unique targets in trypanosome proteome - online
  • PCRPi - Presaging Critical Residues in Protein interfaces-Web server implements a recently described and highly accurate computational tool designed to predict critical residues in protein interfaces - online
  • CPORT - An algorithm for the prediction of protein-protein interface residues - online
  • PIC - Protein Interactions Calculator - Protein-protein energy computation, online, structural analysis
  • DrugscorePPI - A knowledge-based scoring function for computational alanine-scanning in protein-protein interfaces - Hot-Spots online
  • ANCHOR - A web-based tool whose aim is to facilitate the analysis of protein-protein interfaces with regard to its suitability for small molecule drug design - Hot-Spots online
  • KFC - KFC Server: interactive forecasting of protein interaction hot spots - Hot-Spots online
  • HotSprint - Database of computational hot spots in protein interfaces - Hot-Spots
  • Prism - Prism Protocol - Binding site analysis, prediction, standalone
  • FastContact - A free energy scoring tool for protein protein complex structures - Macromolecular scoring (PPI) online
  • PIER - Prediction of interfaces based on atomic statistical propensities - online
  • SPA-PP - Scoring function, specificity and affinity of the protein-protein interactions (algorithm is implemented in C language Bioinformatics, 2013 29:1127-33) - standalone
  • meta-PPISP - Meta server for interface prediction using cons- PPISP, PINUP and Promate - online
  • pyDockNIP - Prediction of binding hot-spots from docking. pyDock module ODA could be use to predict interface regions - online
  • FTMap - Computational solvent mapping is a powerful tool to understand interactions between proteins and solvent molecules. It docks small organic molecules on a protein surface, finds favorable binding positions, clusters the conformations of all prediction, and ranks the clusters on the basis of their average free energy. The low energy clusters are grouped into consensus sites and the largest consensus sites are of interest. The docked fragments can also be served as the building blocks for fragment-based drug design. There is an option to turn on for PPI interaction - online
  • FOLDEF - Energy-based alanine-scanning of a protein complex structure - online
  • HotPoint - Prediction of binding hot-spots based on accessibility and knowledge-based potentials - hotspot
  • ISIS - Sequence-based neural network method for prediciton of binding hot-spot residues and interface residues (first for interface residues but can help for hotspots) - .
  • ROBETTA - Should be able to do Ala scan for hotspot predictions - .
  • KFC2 - The original KFC Server (Knowledge-based FADE and Contacts) predicted binding hotspots within protein-protein interfaces by recognizing structural features indicative of important binding contacts is now KFC2 (with option of Rosetta Ala scan) (need structure of the complex) - .
  • MAPPIS - Recognizes spatially conserved chemical interactions shared by a set of PPIs (needs 3D structure) Multiple Alignment of Protein-Protein InterfaceS (PPIs). (Evolutionary conservation, the tool aims to analyze protein-protein interactions) - .
  • pyDockNIP - pyDockNIP predict hotspots using 2 unbound protein structures via the pyDock tool - standalone
  • ProMate - Prediction of potential protein-protein binding sites for unbound proteins - Binding site prediction online
  • WHISCY - interface prediction based on conservation and surface properties - online
  • ODA - ODA (Optimal Docking Areas), the server is possibly down, please contact Molsoft - Binding site prediction online
  • Link - PPI databases, tools many Links - .
  • PLATINUM - Designed for calculation of hydrophobic properties of molecules and their match or mismatch in receptor-ligand complexes. These properties may help to analyze results of molecular docking - .
  • PresCont - Predicting protein-protein interfaces utilizing four residue properties - .
  • Link - Analysis of interatomic Contacts in Ligand-Protein complexes Analysis of interatomic contacts in protein entries - Analysis of interatomic Contacts
  • SCOWLP - A web-based relational database formed by eleven tables describing PDB interface interactions. The new update also includes 3D classification of protein-protein, -peptide, -saccharide and -nucleic acid interactions, and structure-based binding inferences across folds - Interfaces - databases online
  • ADP_EM - Makes it possible to accurately dock atomic structures into low-resolution electron-density maps - Docking in electron-density maps derived from for instance electron microscopy standalone
  • FADE - See also The Fast Atomic Density Evaluator (FADE) and Pairwise Atomic Density Reverse Engineering (PADRE). Many tools - Predict binding sites and analyze docked complexes
  • 3did - A collection of domain-domain interaction structures and catalogue of domain-peptide structural motifs in the PDB - online
  • HotSpot Wizard - A web server for identification of hot spots - online
  • ConSurf - Enables the identification of functionally important regions on the surface of a protein or domain, of known three-dimensional (3D) structure, based on the phylogenetic relations between its close sequence homologues - online
  • Rate4Site - Detects conserved amino-acid sites by computing the relative evolutionary rate for each site in the multiple sequence alignment - standalone
  • Firestar - Prediction of functionally important residues - online
  • 2P2I - The 2P2I Database, list of complexes and druggability prediction of the interface - online
  • PPI-HitProfiler - In silico filter to build a compound collection enriched in PPI inhibitors (CDithem) - standalone and online via FAF-Drugs3
  • iPPI-DB - Contains 1600 non-peptidic inhibitors (iPPI) accross 12 classes of protein-protein interactions (PPI). The chemical structures of iPPI are manually extracted from the literature (peer-reviewed articles or world patents) along with their phamacological profile and store in iPPI-DB (CDithem project) - curated database
  • TIMBAL - Atomic Interactions and Profile of Small Molecules Disrupting PPI Interfaces: the TIMBAL Database - database
  • AnchorQuery - Is a specialized pharmacophore search technology that brings interactive virtual screening of novel protein-protein inhibitors to the desktop - Protein-protein inhibitors online
  • ProMateus - An open research approach to protein-binding sites analysis - Mutation and docking/binding online
  • HyPare - Tool based on the PARE algorithm (Predicting Association Rate Enhancement). With HyPare you can find hotspots for association, and thus, engineer molecules... - Mutation and docking/binding online
  • OCA - A browser-database for protein structure/function - Structural Analysis, online
  • PARE - The program calculates the change in rate of association (kon) of mutant protein-protein interaction complexes from the change in the Debye Huckel energy of interaction - Structural Analysis, binding, mutations, online
  • NOXclass - Prediction of protein-protein interaction types (biological obligate, biological non-obligate and crystal packing) implemented using a support vector machine (SVM) algorithm - online
  • DILIMOT - A server for finding short (3-8 amino acids), over-represented peptide patterns, or Linear motifs, in a set of proteins - online
  • SLiMFinder - A web server to find novel, significantly over-represented, short protein motifs - online
  • ELM - A computational biology resource for investigating candidate functional sites in eukarytic proteins. Functional site prediction using as input aa sequence. Can be used to search PPI - online
  • PIE - PIE (Protein Interaction information Extraction) - information about PPI
  • Last updated on .

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© Bruno Villoutreix. A first version of this Website was launched in 2006. Thank to Natacha Oliveira