{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T02:29:39Z","timestamp":1793672979538,"version":"4.5.1"},"reference-count":58,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2017,1,17]],"date-time":"2017-01-17T00:00:00Z","timestamp":1484611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The accuracy of five docking programs at reproducing crystallographic structures of complexes of 8 macrolides and 12 related macrocyclic structures, all with their corresponding receptors, was evaluated. Self-docking calculations indicated excellent performance in all cases (mean RMSD values \u2264 1.0) and confirmed the speed of AutoDock Vina. Afterwards, the lowest-energy conformer of each molecule and all the conformers lying 0\u201310 kcal\/mol above it (as given by Macrocycle, from MacroModel 10.0) were subjected to standard docking calculations. While each docking method has its own merits, the observed speed of the programs was as follows: Glide 6.6 &gt; AutoDock Vina 1.1.2 &gt; DOCK 6.5 &gt;&gt; AutoDock 4.2.6 &gt; AutoDock 3.0.5. For most of the complexes, the five methods predicted quite correct poses of ligands at the binding sites, but the lower RMSD values for the poses of highest affinity were in the order: Glide 6.6 \u2248 AutoDock Vina \u2248 DOCK 6.5 &gt; AutoDock 4.2.6 &gt;&gt; AutoDock 3.0.5. By choosing the poses closest to the crystal structure the order was: AutoDock Vina &gt; Glide 6.6 \u2248 DOCK 6.5 \u2265 AutoDock 4.2.6 &gt;&gt; AutoDock 3.0.5. Re-scoring (AutoDock 4.2.6\/\/AutoDock Vina, Amber Score and MM-GBSA) improved the agreement between the calculated and experimental data. For all intents and purposes, these three methods are equally reliable.<\/jats:p>","DOI":"10.3390\/molecules22010136","type":"journal-article","created":{"date-parts":[[2017,1,18]],"date-time":"2017-01-18T10:00:47Z","timestamp":1484733647000},"page":"136","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":199,"title":["The Performance of Several Docking Programs at Reproducing Protein\u2013Macrolide-Like Crystal Structures"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8360-8027","authenticated-orcid":false,"given":"Alejandro","family":"Castro-Alvarez","sequence":"first","affiliation":[{"name":"Organic Chemistry Section, Facultat de Qu\u00edmica, Diagonal 645, Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Costa","sequence":"additional","affiliation":[{"name":"Organic Chemistry Section, Facultat de Qu\u00edmica, Diagonal 645, Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaume","family":"Vilarrasa","sequence":"additional","affiliation":[{"name":"Organic Chemistry Section, Facultat de Qu\u00edmica, Diagonal 645, Universitat de Barcelona, 08028 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,1,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nchembio.1584","article-title":"How proteins bind macrocycles","volume":"10","author":"Villar","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1021\/acschembio.5b00663","article-title":"Dynamic docking of conformationally constrained macrocycles: Methods and applications","volume":"11","author":"Allen","year":"2016","journal-title":"ACS Chem. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3086","DOI":"10.1002\/(SICI)1521-3773(19991018)38:20<3086::AID-ANIE3086>3.0.CO;2-D","article-title":"High-yielding enantioselective synthesis of the macrolactam aglycon of Sch 38516 from two units of (2R)-2-ethyl-4-penten-1-ol","volume":"38","author":"Mas","year":"1999","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3198","DOI":"10.1021\/ol901030f","article-title":"Efficient approach to fluvirucins B2\u2013B5, Sch 38518, and Sch 39185. First synthesis of their aglycon, via CM and RCM reactions","volume":"11","author":"Vilarrasa","year":"2009","journal-title":"Org. Lett."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5191","DOI":"10.1021\/ol8021676","article-title":"Stereocontrolled total synthesis of amphidinolide X via a silicon-tethered metathesis reaction","volume":"10","author":"Vilarrasa","year":"2008","journal-title":"Org. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.tetlet.2013.12.047","article-title":"Synthesis of amphidinolide Y precursors","volume":"55","author":"Mola","year":"2014","journal-title":"Tetrahedron Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4083","DOI":"10.1021\/ol051200o","article-title":"Synthesis of (\u2212)-amphidinolide K fragment C9\u2013C22","volume":"7","author":"Andreou","year":"2005","journal-title":"Org. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4843","DOI":"10.1021\/ol801923y","article-title":"Synthesis of amphidinolide E C10\u2212C26 fragment","volume":"10","author":"Esteban","year":"2008","journal-title":"Org. Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4934","DOI":"10.1021\/ol2020187","article-title":"Iododesilylation of TIPS-, TBDPS-, and TBS-substituted alkenes in connection with the synthesis of amphidinolides B\/D","volume":"13","author":"Sidera","year":"2011","journal-title":"Org. Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4623","DOI":"10.1016\/j.tetlet.2014.06.066","article-title":"A synthetic approach to palmerolides via Negishi cross coupling. The challenge of the C15\u2013C16 bond formation","volume":"55","author":"Carrillo","year":"2014","journal-title":"Tetrahedron Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4825","DOI":"10.1016\/j.bmcl.2004.07.053","article-title":"Computational comparison of microtubule-stabilising agents laulimalide and peloruside with taxol and colchicine","volume":"14","author":"Pineda","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nchembio853","article-title":"Cyclostreptin binds covalently to microtubule pores and lumenal taxoid binding sites","volume":"3","author":"Buey","year":"2007","journal-title":"Nat. Chem. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1002\/cbic.201000294","article-title":"Molecular recognition of peloruside A by microtubules. The C24 primary alcohol is essential for biological activity","volume":"11","author":"Pera","year":"2010","journal-title":"ChemBioChem"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1002\/cbic.201100042","article-title":"Mechanism of action of the cytotoxic macrolides amphidinolide X and J","volume":"12","author":"Trigili","year":"2011","journal-title":"ChemBioChem"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1021\/bi201380p","article-title":"Cyclostreptin derivatives specifically target cellular tubulin and further map the paclitaxel site","volume":"51","author":"Calvo","year":"2012","journal-title":"Biochemistry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.tips.2014.12.001","article-title":"Beware of docking!","volume":"36","author":"Chen","year":"2015","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"10150","DOI":"10.3390\/molecules190710150","article-title":"Challenges, applications, and recent advances of protein-ligand docking in structure-based drug design","volume":"19","author":"Grinter","year":"2014","journal-title":"Molecules"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.2174\/0929867311320180002","article-title":"Protein-ligand docking in the new millennium\u2014A retrospective of 10 years in the field","volume":"20","author":"Sousa","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/jmr.2266","article-title":"Latest developments in molecular docking: 2010\u20132011 in review","volume":"26","author":"Yuriev","year":"2013","journal-title":"J. Mol. Recognit."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/jcc.21643","article-title":"Can we trust docking results? Evaluation of seven commonly used programs on PDBbind database","volume":"32","author":"Plewczynski","year":"2011","journal-title":"J. Comput. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1186\/1479-7364-5-5-497","article-title":"Survey of public domain software for docking simulations and virtual screening","volume":"5","author":"Biesiada","year":"2011","journal-title":"Hum. Genom."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/jmr.1077","article-title":"Challenges and advances in computational docking: 2009 in review","volume":"24","author":"Yuriev","year":"2011","journal-title":"J. Mol. Recognit."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.3390\/ijms11083016","article-title":"Advances and challenges in protein\u2013ligand docking","volume":"11","author":"Huang","year":"2010","journal-title":"Int. J. Mol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1002\/jcc.21498","article-title":"Evaluation of the performance of four molecular docking programs on a diverse set of protein-ligand complexes","volume":"31","author":"Li","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1021\/ci900056c","article-title":"Comparison of several molecular docking programs: Pose prediction and virtual screening accuracy","volume":"49","author":"Cross","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s10822-007-9163-6","article-title":"Evaluation of the performance of 3D virtual screening protocols: RMSD comparisons, enrichment assessments, and decoy selection\u2014What can we learn from earlier mistakes?","volume":"22","author":"Kirchmair","year":"2008","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1021\/ci7000378","article-title":"Evaluations of molecular docking programs for virtual screening","volume":"47","author":"Onodera","year":"2007","journal-title":"J. Chem. Inf. Model."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1002\/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B","article-title":"Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function","volume":"19","author":"Morris","year":"1998","journal-title":"J. Comput. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1541007","DOI":"10.1142\/S0219720015410073","article-title":"PSOVina: The hybrid particle swarm optimization algorithm for protein\u2013ligand docking","volume":"13","author":"Ng","year":"2015","journal-title":"J. Bioinform. Comput. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1261\/rna.1563609","article-title":"DOCK 6: Combining techniques to model RNA-small molecule complexes","volume":"15","author":"Lang","year":"2009","journal-title":"RNA"},{"key":"ref_33","unstructured":"(2013). Glide, Schr\u00f6dinger, LLC. Version 5.9."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1021\/ja1023817","article-title":"Dictyostatin flexibility bridges conformations in solution and in the \u03b2-tubulin taxane binding site","volume":"133","author":"Jogalekar","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.jmb.2008.11.010","article-title":"RosettaLigand docking with full ligand and receptor flexibility","volume":"385","author":"Davis","year":"2009","journal-title":"J. Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/nchembio.1768","article-title":"The structure of SpnF, a standalone enzyme that catalyzes [4 + 2] cycloaddition","volume":"11","author":"Fage","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1007\/s10822-016-9973-5","article-title":"Predicting bioactive conformations and binding modes of macrocycles","volume":"30","author":"Anighoro","year":"2016","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1021\/ci5001086","article-title":"The application of statistical methods of cognate docking: A path forward?","volume":"54","author":"Hawkins","year":"2014","journal-title":"J. Chem. Inf. Mod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.compbiolchem.2016.04.005","article-title":"Machine learning optimization of cross docking accuracy","volume":"62","author":"Bjerrum","year":"2016","journal-title":"Comput. Biol. Chem."},{"key":"ref_40","first-page":"58","article-title":"Molecular docking studies of 1,3,4-thiadiazoles as novel peptide deformylase inhibitors as potential antibacterial agents","volume":"31","author":"Vadivelu","year":"2015","journal-title":"Int. J. Pharm. Sci. Rev. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/minf.201400132","article-title":"Improving AutoDock Vina using random forest: The growing accuracy of binding affinity prediction by the effective exploitation of larger data sets","volume":"34","author":"Li","year":"2015","journal-title":"Mol. Inform."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1021\/ci5003735","article-title":"Improving docking results via reranking of ensembles of ligand poses in multiple X-ray protein conformations with MM-GBSA","volume":"54","author":"Greenidge","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1021\/ci400042y","article-title":"Comparing neural-network scoring functions and the state of the art: Applications to common library screening","volume":"53","author":"Durrant","year":"2013","journal-title":"J. Chem. Inf. Model."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4236\/cmb.2013.32004","article-title":"BEAR, a molecular docking refinement and rescoring method","volume":"3","author":"Anighoro","year":"2013","journal-title":"Comput. Mol. Biosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/minf.201100141","article-title":"Molecular docking study based on pharmacophore modeling for novel phosphodiesterase IV inhibitors","volume":"31","author":"Aviyente","year":"2012","journal-title":"Mol. Inform."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4661","DOI":"10.1016\/j.ejmech.2011.05.026","article-title":"Consensus virtual screening approaches to predict protein ligands","volume":"46","author":"Kukol","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1021\/jm0203783","article-title":"Comparative evaluation of 11 scoring functions for molecular docking","volume":"46","author":"Wang","year":"2003","journal-title":"J. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"19824","DOI":"10.1021\/jp961710n","article-title":"Parametrized models of aqueous free energies of solvation based on pairwise descreening of solute atomic charges from a dielectric medium","volume":"100","author":"Hawkins","year":"1996","journal-title":"J. Phys. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/1097-0282(2000)56:4<275::AID-BIP10024>3.0.CO;2-E","article-title":"Theory and applications of the generalized born solvation model in macromolecular simulations","volume":"56","author":"Tsui","year":"2000","journal-title":"Biopolymers"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.jmb.2008.01.049","article-title":"Rescoring docking hit lists for model cavity sites: Predictions and experimental testing","volume":"377","author":"Graves","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_52","unstructured":"PRIME MM-GBSA. Available online: https:\/\/www.schrodinger.com\/kb\/1484."},{"key":"ref_53","first-page":"1000","article-title":"Comparison of automatic three-dimensional model builders using 639 X-ray structures","volume":"34","author":"Sadowski","year":"1994","journal-title":"J. Chem. Inf. Model."},{"key":"ref_54","unstructured":"LigPrep. Available online: https:\/\/www.schrodinger.com\/ligprep."},{"key":"ref_55","unstructured":"(2013). MacroModel, Schr\u00f6dinger. Version 10.0."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7898","DOI":"10.1016\/j.bmc.2013.10.003","article-title":"Tackling the conformational sampling of larger flexible compounds and macrocycles in pharmacology and drug discovery","volume":"21","author":"Chen","year":"2013","journal-title":"Bioorg. Med. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2680","DOI":"10.1021\/ci5001696","article-title":"Macrocycle conformational sampling with MacroModel","volume":"54","author":"Watts","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/1\/136\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:26:24Z","timestamp":1760207184000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/1\/136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,17]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,1]]}},"alternative-id":["molecules22010136"],"URL":"https:\/\/doi.org\/10.3390\/molecules22010136","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,17]]}}}