Another direction to look for an active site residues could be to find a homologous protein and see if there is any data available regarding its active site or even to look for a protein from the same family. Such an approach might provide you some lead then you could combine that with software's output and see if there is any correlation between them or not.

One more way is to use AutoDock. You create the PDB file of your desired ligand in ProDrg or in some other software and run AutoDock either on the entire protein structure or on the specified positions. Based on the results, you can actually identify the interacting residues and position of ligand binding.

Follow the attached link:

https://www.researchgate.net/post/Best_free_tool_to_identify_the_active_site_of_the_protein2

Good luck

would recommend to use the pubsum server firstly to know more about your protein !

castP or metapocket can can help you find the binding residues of your protein.

Hello there

you can use from these webservers for finding binding site of protein and interacting residues in protein protein

https://bip.weizmann.ac.il/toolbox/structure/binding.htm#pp

http://consurf.tau.ac.il/2016/

http://pocketquery.csb.pitt.edu/

http://milou.science.uu.nl/services/CPORT/

http://mordred.bioc.cam.ac.uk/~crescendo/crescendo.php

http://pipe.scs.fsu.edu/ppisp.html

I hope that the problem of protein folding and also finding the binding site of protein will soon solved with molecular dynamics simulation (gromacs).

sincerely

good luck

https://www.researchgate.net/post/Best_free_tool_to_identify_the_active_site_of_the_protein2

Hello,

Try using Sietmap from Schrodinger..That may help you in providing the D-scores and Site scores and help you to get druggability sites and ligand binding sites.

CASTp

http://sts.bioe.uic.edu/castp/calculation.html

Its free easy, simple and yet efficient one.

Try BSP-SLIM sever. Sitemap is also great.

Software

• MED-SuMo. Program for macromolecules surface similarity detection. Searches into 3D databases, find similar binding surfaces and generate 3D superpositions based on common surface chemical features and similar shape. Can be used for site mining, drug repurposing and site classification at PDB scale. Distributed by MEDIT.
• TRAPP. TRAnsient Pockets in Proteins (TRAPP) is a web server for the analysis of transient binding pockets in proteins. Contrarily to many tools, it is not intended for ligand binding pocket identification per se, but rather to predict significant changes in the spatial and physicochemical properties of a given pocket that may arise due to the protein's flexibility (both backbone and side chains). Several capabilities of visualization and analysis have been developed and are provided by the Molecular and Cellular Modeling group at Heidelberg Institute for Theoretical Studies, Germany.
• CAVER. Software tool for analysis and visualisation of tunnels and channels in protein structures. Provided by the Masaryk University.
• fpocket. Open source protein pocket (cavity) detection algorithm based on Voronoi tessellation. Developed in the C programming language and currently available as command line driven program. fpocket includes two other programs (dpocket & tpocket) that allow you to extract pocket descriptors and test own scoring functions respectively. Also contains a druggability prediction score.
• GHECOM. Program for finding multi-scale pockets on protein surfaces using mathematical morphology. Free open source.
• LIGSITEcsc. Program for the automatic identification of pockets on protein surface using the Connolly surface and the degree of conservation.
• SURFNET. Generates surfaces and void regions between surfaces from coordinate data supplied in a PDB file.
• SiteHound. Identifies ligand binding sites by computing interactions between a chemical probe and a protein structure. The input is a PDB file of a protein structure, the output is a list of “interaction energy clusters” corresponding to putative binding sites.
• ICM-PocketFinder. Binding site predictor based on calculating the drug-binding density field and contouring it at a certain level. Provided by Molsoft.
• SiteMap. Program for binding site identification. Distributed by Schrodinger.
• MSPocket. Orientation independent program for the detection and graphical analysis of protein surface pockets. A MSPocket plugin for PyMOL provides a graphical user interface for runing MSPocket and render its results in PyMOL. It is included in the download. Free and open source.
• POCASA. (POcket-CAvity Search Application). Automatic web service that implements the algorithm named Roll which can predict binding sites by detecting pockets and cavities of proteins of known 3D structure. Maintained by the Hokkaido University.
• Phosfinder. Method for the prediction of phosphate-binding sites in protein structures. provided by the University of Rome.
• VOIDOO. Software to find cavities and analyse volumes.
• FunFOLDQA. Program to assess the quality ligand binding site residue predictions based on 3D models of proteins. Free program written in java. Developped by the University of Reading.
• LISE. Free and open source program for ligand Binding Site Prediction Using Ligand Interacting and Binding Site-Enriched Protein Triangles. Exists as a web service. Provided by the Institute of Biomedical Sciences, Academia Sinica.
• PDBinder. Free program for the identification of small ligand-binding sites in a protein structure. webPDBinder searches a protein structure against a library of known binding sites and a collection of control non-binding pockets. Exists as a web service. Provided by the University of Roma 2, Italy.
• eFindSite. Ligand binding site prediction and virtual screening algorithm that detects common ligand binding sites in a set of evolutionarily related proteins identified by 10 threading/fold recognition methods. Exists as a web service. Provided by the Louisiana State University, Computational Systems Biology Group.
• POVME. Free and open source program for measuring binding-pocket volumes. Developed by the National Biomedical Computation Resource.
• SiteEngine. Program to predict regions that can potentially function as binding sites. The methods is based on recognition of geometrical and physico-chemical environments that are similar to known binding sites. Exists as a web service. Provided by the structural Bioinformatics group at Tel-Aviv University.
• SVILP_ligand. General method for discovering the features of binding pockets that confer specificity for particular ligands. Provided by the Computational Bioinformatics Laboratory, Imperial College London.

Databases

• sc-PDB. Annotated Database of Druggable Binding Sites from the Protein DataBank. Provided by the university of Strasbourg.
• CASTp. Computed Atlas of Surface Topography of proteins. Provides identification and measurements of surface accessible pockets as well as interior inaccessible cavities, for proteins and other molecules. castP server uses the weighted Delaunay triangulation and the alpha complex for shape measurements.
• Pocketome. Encyclopedia of conformational ensembles of all druggable binding sites that can be identified experimentally from co-crystal structures in the Protein Data Bank.
• PDBe motifs and Sites. Can be used to examine the characteristics of the binding sites of single proteins or classes of proteins such as Kinases and the conserved structural features of their immediate environments either within the same specie or across different species.
• LigASite. Dataset of biologically relevant binding sites in protein structures. It consists of proteins with one unbound structure and at least one structure of the protein-ligand complex. Both a redundant and a non-redundant (sequence identity lower than 25%) version is available.
• PROtein SURFace ExploreR. Contains information about structural similarities with respect to the query surfaces. A pocket search algorithm detected 48,347 potential ligand binding sites from the 9,708 non-redundant protein entries in the PDB database. All-against-all structural comparison was performed for the predicted sites, and the similar sites with the Z-score ≥ 2.5 were selected. These results can be accessed by the PDB code or ligand name.
• fPOP. Footprinting protein functional surfaces by comparative spatial patterns. Database of the protein functional surfaces identified by shape analysis.
• PDBSITE. Database on protein active sites and their spatial environment. Provided by GeneNetworks.
• LigBase. Database of ligand binding proteins aligned to structural templates. The structural templates are taken from the PDB, 3D models of the aligned sequences are provided ModBase, and pairwise sequence alignments are provided by CE. Multiple Structural Alignments are built on the fly within LigBase from a series of pairwise alignments. Ligand diagrams are generated with the program Ligplot. Maintained by Andrej Sali at the University of California, San Francisco.

Web services

• 3DLigandSite. Automated method for the prediction of ligand binding sites. Provided by the Imperial London College.
• metaPocket. Meta server to identify pockets on protein surface to predict ligand-binding sites.
• PockDrug. A methodology tehat predicts pocket druggability, efficient on both; estimated pockets guided by the ligand proximity (extracted by proximity to a ligand from a holo protein structure using several thresholds) and estimated pockets not guided by the ligand proximity (based on amino atoms that form the surface of potential binding cavities).. Developed and maintained by the University Paris-Diderot, France.
• PocketQuery. Protein-protein interaction (PPI) inhibitor starting points from PPI structure. Quickly identify a small set of residues at a protein interface that are suitable starting points for small-molecule design. Provided by the University of Pittsburgh.
• PASS. Program for tentative identification of drug interaction pockets from protein structure.
• DEPTH. Web server to compute depth and predict small-molecule binding cavities in proteins
• fpocket web server. Open source protein pocket (cavity) detection algorithm based on Voronoi tessellation. Developed in the C programming language and currently available as command line driven program. fpocket includes two other programs (dpocket & tpocket) that allow you to extract pocket descriptors and test own scoring functions respectively. Also contains a druggability prediction score.
• Nucleos. Nucleos is a webserver for the identification of nucleotide-binding sites based on the concept of nucleotide modularity. Nucleos identifies binding sites for nucleotide modules (namely the nucleobase, the carbohydrate and the phosphate) and then combines them in order to build the complete binding sites for different types of nucleotides (e.g. ADP or FAD). Provided by the University of Roma 2, Italy.
• wwwPDBinder. Web server for the identification of small ligand-binding sites in a protein structure. webPDBinder searches a protein structure against a library of known binding sites and a collection of control non-binding pockets. Exists as a standalone program. Provided by the University of Roma 2, Italy.
• IsoMIF. IsoMIF identifies binding site molecular interaction field similarities between proteins. The IsoMIF Finder Interface allows you to identify binding site molecular interaction field (MIF) similarities between a query structure and a database of pre-calculated MIFs or you own custom PDB entries. Developed by the University of Sherbrooke, Canada.
• LISE. Ligand Binding Site Prediction Using Ligand Interacting and Binding Site-Enriched Protein Triangles. Exists as a standalone program. Provided by the Institute of Biomedical Sciences, Academia Sinica.
• eFindSite. Web server for ligand binding site prediction and virtual screening algorithm that detects common ligand binding sites in a set of evolutionarily related proteins identified by 10 threading/fold recognition methods. Exists as standalone program. Provided by the Louisiana State University, Computational Systems Biology Group.
• Active Site Prediction. Web server for computing the cavities in a given protein. Provided by the Supercomputing Facility for Bioinformatics & Computational Biology, IIT Delhi.
• GHECOM web server. Web server for finding multi-scale pockets on protein surfaces using mathematical morphology.
• LIGSITEcsc web server. Web server for the automatic identification of pockets on protein surface using the Connolly surface and the degree of conservation.
• ProBis. Web server for detection of structurally similar binding sites. Maintained by the National Institute of Chemistry, Ljubljana, Slovenia.
• ProBiS-CHARMMing. Web server for detection of structurally similar binding sites, plus minimization of predicted protein-ligand complexes and their interaction energy calculation. Maintained by the National Institute of Health, USA.
• FunFOLD. Web server to predict likely ligand binding site residues for a submitted amino acid sequence.
• CAVER. Software tool for analysis and visualisation of tunnels and channels in protein structures. Provided by the Masaryk University.
• SuMo. Screens the Protein Data Bank (PDB) for finding ligand binding sites matching your protein structure or inversely, for finding protein structures matching a given site in your protein. Provided freely by the Pole Bioinformatique Lyonnais.
• IBIS. (Inferred Biomolecular Interactions Server). For a given protein sequence or structure query, IBIS reports physical interactions observed in experimentally-determined structures for this protein. IBIS also infers/predicts interacting partners and binding sites by homology, by inspecting the protein complexes formed by close homologs of a given query.
• PocketDepth. Depth based algortihm for identification of ligand binding sites.
• Screen2. Tool for identifying protein cavities and computing cavity attributes that can be applied for classification and analysis.
• SiteHound-web. Identifies ligand binding sites by computing interactions between a chemical probe and a protein structure. The input is a PDB file of a protein structure, the output is a list of “interaction energy clusters” corresponding to putative binding sites. Maintained by the Sanchez lab, at the Mount Sinai School of Medicine, NY, USA.
• SiteComp. Web server providing three major types of analysis based on molecular interaction fields: binding site comparison, binding site decomposition and multi-probe characterization. Maintained by the Sanchez lab, at the Mount Sinai School of Medicine, NY, USA.
• ConCavity. Ligand binding site prediction from protein sequence and structure.
• SplitPocket. Prediction of binding sites for unbound structures.
• PepSite 2. Web service for the prediction of peptide binding sites on protein surfaces. Developed and maintained by the Russel Lab, University of Heidelberg.
• MolAxis. Web server for the identification of channels in macromolecules.
• PDBSiteScan. Tool for search for functional sites in protein tertiary structures. Developed in collaboration with Institute of Cytology and Genetics, Novosibirsk.
• MultiBind. (Multiple Alignment of Protein Binding Sites). Prediction tool for protein binding sites. Users input a set of protein-small molecule complexes and MultiBind predicts the common physio-chemical patterns responsible for protein binding. Exists as a standalone program. Provided by the structural Bioinformatics group at Tel-Aviv University.
• SiteEngine. Web service to predict regions that can potentially function as binding sites. The methods is based on recognition of geometrical and physico-chemical environments that are similar to known binding sites. Exists as a standalone program. Provided by the structural Bioinformatics group at Tel-Aviv University