{"id":883,"date":"2019-04-17T21:14:56","date_gmt":"2019-04-17T21:14:56","guid":{"rendered":"https:\/\/ccsb.scripps.edu\/adfr\/?page_id=883"},"modified":"2019-10-30T23:03:19","modified_gmt":"2019-10-30T23:03:19","slug":"flexible-receptor","status":"publish","type":"page","link":"https:\/\/ccsb.scripps.edu\/adfr\/flexible-receptor\/","title":{"rendered":"Tutorial flexible receptor"},"content":{"rendered":"<p class=\"last-modified\">This page was last updated on October 30th, 2019 at 11:03 pm<\/p><div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-1 nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-0 fusion_builder_column_1_1 1_1 fusion-one-full fusion-column-first fusion-column-last\" style=\"--awb-bg-size:cover;\"><div class=\"fusion-column-wrapper fusion-flex-column-wrapper-legacy\"><div class=\"fusion-text fusion-text-1\"><h3>Docking a flexible ligand into a receptor with flexible side chains<\/h3>\n<p>In this tutorial we illustrate how to re-dock a known ligand into its native receptor.\u00a0We will use the cyclic dependent kinase protein 2 CDK2 (pdbid:4EK3) and one of its ligands (pdbid:4EK4).<\/p>\n<p><strong>In this tutorial you will learn<\/strong>:<\/p>\n<ul>\n<li>to compute affinity maps for a pocket with flexible receptor side chains<\/li>\n<li>to run ADFR to re-dock the ligand into the receptor with 3 flexible side chains<\/li>\n<\/ul>\n<\/div><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-separator fusion-full-width-sep\" style=\"margin-left: auto;margin-right: auto;margin-top:15px;margin-bottom:25px;width:100%;\"><div class=\"fusion-separator-border sep-shadow\" style=\"--awb-height:20px;--awb-amount:20px;background:radial-gradient(ellipse at 50% -50% , #e0dede 0px, rgba(255, 255, 255, 0) 80%) repeat scroll 0 0 rgba(0, 0, 0, 0);background:-webkit-radial-gradient(ellipse at 50% -50% , #e0dede 0px, rgba(255, 255, 255, 0) 80%) repeat scroll 0 0 rgba(0, 0, 0, 0);background:-moz-radial-gradient(ellipse at 50% -50% , #e0dede 0px, rgba(255, 255, 255, 0) 80%) repeat scroll 0 0 rgba(0, 0, 0, 0);background:-o-radial-gradient(ellipse at 50% -50% , #e0dede 0px, rgba(255, 255, 255, 0) 80%) repeat scroll 0 0 rgba(0, 0, 0, 0);\"><\/div><\/div><div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-tabs fusion-tabs-1 clean vertical-tabs icon-position-left mobile-mode-accordion\" style=\"--awb-title-border-radius-top-left:0px;--awb-title-border-radius-top-right:0px;--awb-title-border-radius-bottom-right:0px;--awb-title-border-radius-bottom-left:0px;--awb-inactive-color:#9acae0;--awb-background-color:#ffffff;--awb-border-color:#9acae0;--awb-active-border-color:#d65169;\"><div class=\"nav\"><ul class=\"nav-tabs\" role=\"tablist\"><li class=\"active\" role=\"presentation\"><a class=\"tab-link\" data-toggle=\"tab\" role=\"tab\" aria-controls=\"tab-3237c8ae924013299c3\" aria-selected=\"true\" id=\"fusion-tab-generatetargetfile\" href=\"#tab-3237c8ae924013299c3\"><h4 class=\"fusion-tab-heading\"><i class=\"fontawesome-icon fa-cogs fas\" aria-hidden=\"true\" style=\"font-size:13px;\"><\/i>Generate target file<\/h4><\/a><\/li><li role=\"presentation\"><a class=\"tab-link\" data-toggle=\"tab\" role=\"tab\" aria-controls=\"tab-af1607d5f15e9e0daf7\" aria-selected=\"false\" tabindex=\"-1\" id=\"fusion-tab-targetfilemeta-data\" href=\"#tab-af1607d5f15e9e0daf7\"><h4 class=\"fusion-tab-heading\"><i class=\"fontawesome-icon fa-search fas\" aria-hidden=\"true\" style=\"font-size:13px;\"><\/i>Target file meta-data<\/h4><\/a><\/li><li role=\"presentation\"><a class=\"tab-link\" data-toggle=\"tab\" role=\"tab\" aria-controls=\"tab-d54314ff1af0a31f795\" aria-selected=\"false\" tabindex=\"-1\" id=\"fusion-tab-dockingtheligand\" href=\"#tab-d54314ff1af0a31f795\"><h4 class=\"fusion-tab-heading\"><i class=\"fontawesome-icon fa-cogs fas\" aria-hidden=\"true\" style=\"font-size:13px;\"><\/i>Docking the ligand<\/h4><\/a><\/li><li role=\"presentation\"><a class=\"tab-link\" data-toggle=\"tab\" role=\"tab\" aria-controls=\"tab-38c0c3e418cf263d8c1\" aria-selected=\"false\" tabindex=\"-1\" id=\"fusion-tab-understandingtheoutput\" href=\"#tab-38c0c3e418cf263d8c1\"><h4 class=\"fusion-tab-heading\"><i class=\"fontawesome-icon fa-lightbulb far\" aria-hidden=\"true\" style=\"font-size:13px;\"><\/i>Understanding the output<\/h4><\/a><\/li><\/ul><\/div><div class=\"tab-content\"><div class=\"nav fusion-mobile-tab-nav\"><ul class=\"nav-tabs\" role=\"tablist\"><li class=\"active\" role=\"presentation\"><a class=\"tab-link\" data-toggle=\"tab\" role=\"tab\" aria-controls=\"tab-3237c8ae924013299c3\" aria-selected=\"true\" id=\"mobile-fusion-tab-generatetargetfile\" href=\"#tab-3237c8ae924013299c3\"><h4 class=\"fusion-tab-heading\"><i class=\"fontawesome-icon fa-cogs fas\" aria-hidden=\"true\" style=\"font-size:13px;\"><\/i>Generate target file<\/h4><\/a><\/li><\/ul><\/div><div class=\"tab-pane fade fusion-clearfix in active\" role=\"tabpanel\" tabindex=\"0\" aria-labelledby=\"fusion-tab-generatetargetfile\" id=\"tab-3237c8ae924013299c3\">\n<h4>Generate the target file containing the affinity maps.<\/h4>\n<p>flexible residues can be specified on the command line using the\u00a0<strong>-f\/&#8211;flexRes<\/strong>\u00a0option with a selection string e.g.\u00a0&#8220;<em>A:ILE10,VAL32;B:SER48<\/em>&#8220;.<\/p>\n<style type=\"text\/css\" scopped=\"scopped\">.fusion-syntax-highlighter-1 > .CodeMirror, .fusion-syntax-highlighter-1 > .CodeMirror .CodeMirror-gutters {background-color:var(--awb-color1);}<\/style><div class=\"fusion-syntax-highlighter-container fusion-syntax-highlighter-1 fusion-syntax-highlighter-theme-light\" style=\"opacity:0;margin-top:0px;margin-right:0px;margin-bottom:15px;margin-left:0px;font-size:14px;border-width:1px;border-style:solid;border-color:var(--awb-color3);\"><div class=\"syntax-highlighter-copy-code\"><span class=\"syntax-highlighter-copy-code-title\" data-id=\"fusion_syntax_highlighter_1\" style=\"font-size:14px;\">Copy to Clipboard<\/span><\/div><label for=\"fusion_syntax_highlighter_1\" class=\"screen-reader-text\">Syntax Highlighter<\/label><textarea class=\"fusion-syntax-highlighter-textarea\" id=\"fusion_syntax_highlighter_1\" data-readOnly=\"nocursor\" data-lineNumbers=\"\" data-lineWrapping=\"\" data-theme=\"default\" data-mode=\"text\/x-sh\">agfr -l data\/4EK4_lig.pdbqt -r data\/4EK3_rec.pdbqt -f A:ILE10,LYS33 -P 8.0 -m ligand -o 4EK3_rec_FR_10_33<\/textarea><\/div>\n<div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-separator fusion-full-width-sep\" style=\"margin-left: auto;margin-right: auto;margin-top:15px;margin-bottom:15px;width:100%;\"><div class=\"fusion-separator-border sep-double sep-solid\" style=\"--awb-height:20px;--awb-amount:20px;border-color:#e0dede;border-top-width:1px;border-bottom-width:1px;\"><\/div><\/div><div class=\"fusion-sep-clear\"><\/div>\n<p><strong>Details<\/strong>: a\u00a0target file for pocket of PDB id 1EK3 binding the crystallographic ligand can be computed using:<\/p>\n<style type=\"text\/css\" scopped=\"scopped\">.fusion-syntax-highlighter-2 > .CodeMirror, .fusion-syntax-highlighter-2 > .CodeMirror .CodeMirror-gutters {background-color:var(--awb-color1);}<\/style><div class=\"fusion-syntax-highlighter-container fusion-syntax-highlighter-2 fusion-syntax-highlighter-theme-light\" style=\"opacity:0;margin-top:0px;margin-right:0px;margin-bottom:0px;margin-left:0px;font-size:14px;border-width:1px;border-style:solid;border-color:var(--awb-color3);\"><div class=\"syntax-highlighter-copy-code\"><span class=\"syntax-highlighter-copy-code-title\" data-id=\"fusion_syntax_highlighter_2\" style=\"font-size:14px;\">Copy to Clipboard<\/span><\/div><label for=\"fusion_syntax_highlighter_2\" class=\"screen-reader-text\">Syntax Highlighter<\/label><textarea class=\"fusion-syntax-highlighter-textarea\" id=\"fusion_syntax_highlighter_2\" data-readOnly=\"nocursor\" data-lineNumbers=\"\" data-lineWrapping=\"\" data-theme=\"default\" data-mode=\"text\/x-sh\">agfr -l data\/4EK4_lig.pdbqt -r data\/4EK3_rec.pdbqt -f A:ILE10,LYS33<\/textarea><\/div>\n<p>However, <em>agfr<\/em> will fail to generate the target file in this case because the docking box defined with the default padding of 4 Angstroms around the ligand is too small to cover the flexible side chains<\/p>\n<style type=\"text\/css\" scopped=\"scopped\">.fusion-syntax-highlighter-3 > .CodeMirror, .fusion-syntax-highlighter-3 > .CodeMirror .CodeMirror-gutters {background-color:var(--awb-color1);}.fusion-syntax-highlighter-3 > .CodeMirror .CodeMirror-gutters { background-color: var(--awb-color2); }.fusion-syntax-highlighter-3 > .CodeMirror .CodeMirror-linenumber { color: var(--awb-color8); }<\/style><div class=\"fusion-syntax-highlighter-container fusion-syntax-highlighter-3 fusion-syntax-highlighter-theme-light\" style=\"opacity:0;margin-top:0px;margin-right:0px;margin-bottom:15px;margin-left:0px;font-size:14px;border-width:1px;border-style:solid;border-color:var(--awb-color3);\"><label for=\"fusion_syntax_highlighter_3\" class=\"screen-reader-text\">Syntax Highlighter<\/label><textarea class=\"fusion-syntax-highlighter-textarea\" id=\"fusion_syntax_highlighter_3\" data-readOnly=\"nocursor\" data-lineNumbers=\"1\" data-lineWrapping=\"\" data-theme=\"default\" data-mode=\"text\/x-sh\">Computing grids on fiji a Darwin-17.7.0-x86_64-i386-64bit computer\nDate Thu Apr 18 11:13:22 2019\n\nloading receptor: data\/4EK3_rec.pdbqt\nloading ligand: data\/4EK4_lig.pdbqt\n\nset box using ligand\n    Box center:    23.332    28.922    29.598\n    Box length:    17.250    16.500    12.000\n    Box size  :        46        44        32\n    padding   :     4.000\n    spacing   :     0.375\nUnable to proceed due to the following error(s):\nFlexible residue(s) A: LYS33  outside the box.\n<\/textarea><\/div>\n<p>To correct this we will increase the padding to 8.0. For reducing calculation time for the tutorial we also tell <em>adfr<\/em> to only compute maps for atom types present in the ligand ( -m ligand), and use the AutoSite 1.0 algorithm -as.<\/p>\n<style type=\"text\/css\" scopped=\"scopped\">.fusion-syntax-highlighter-4 > .CodeMirror, .fusion-syntax-highlighter-4 > .CodeMirror .CodeMirror-gutters {background-color:var(--awb-color1);}<\/style><div class=\"fusion-syntax-highlighter-container fusion-syntax-highlighter-4 fusion-syntax-highlighter-theme-light\" style=\"opacity:0;margin-top:0px;margin-right:0px;margin-bottom:15px;margin-left:0px;font-size:14px;border-width:1px;border-style:solid;border-color:var(--awb-color3);\"><div class=\"syntax-highlighter-copy-code\"><span class=\"syntax-highlighter-copy-code-title\" data-id=\"fusion_syntax_highlighter_4\" style=\"font-size:14px;\">Copy to Clipboard<\/span><\/div><label for=\"fusion_syntax_highlighter_4\" class=\"screen-reader-text\">Syntax Highlighter<\/label><textarea class=\"fusion-syntax-highlighter-textarea\" id=\"fusion_syntax_highlighter_4\" data-readOnly=\"nocursor\" data-lineNumbers=\"\" data-lineWrapping=\"\" data-theme=\"default\" data-mode=\"text\/x-sh\">agfr -l data\/4EK4_lig.pdbqt -r data\/4EK3_rec.pdbqt -f A:ILE10,LYS33 -P 8.0 -m ligand -o 4EK3_rec_FR_10_33<\/textarea><\/div>\n<p>-r : specifies the receptor file<\/p>\n<p>-l : specifies the ligand file<\/p>\n<p>-f : indicates the receptor side chains to be made flexible. These atoms will not contribute to the calculation of the grids. To describe residues in different chains use a semi-colon between residues from different chains&#8221;;&#8221; e.g. &#8220;A:PHE80 ; B:LYS89&#8221;.<\/p>\n<p>-m : specifies that maps should only be calculated for atom types present in the ligand<\/p>\n<p>-o : specifies the name of the target file to create<\/p>\n<h4>The command produces the following output:<\/h4>\n<style type=\"text\/css\" scopped=\"scopped\">.fusion-syntax-highlighter-5 > .CodeMirror, .fusion-syntax-highlighter-5 > .CodeMirror .CodeMirror-gutters {background-color:var(--awb-color1);}.fusion-syntax-highlighter-5 > .CodeMirror .CodeMirror-gutters { background-color: var(--awb-color2); }.fusion-syntax-highlighter-5 > .CodeMirror .CodeMirror-linenumber { color: var(--awb-color8); }<\/style><div class=\"fusion-syntax-highlighter-container fusion-syntax-highlighter-5 fusion-syntax-highlighter-theme-light\" style=\"opacity:0;margin-top:0px;margin-right:0px;margin-bottom:0px;margin-left:0px;font-size:14px;border-width:1px;border-style:solid;border-color:var(--awb-color3);\"><label for=\"fusion_syntax_highlighter_5\" class=\"screen-reader-text\">Syntax Highlighter<\/label><textarea class=\"fusion-syntax-highlighter-textarea\" id=\"fusion_syntax_highlighter_5\" data-readOnly=\"nocursor\" data-lineNumbers=\"1\" data-lineWrapping=\"\" data-theme=\"default\" data-mode=\"text\/x-sh\">#################################################################\n# If you used AGFR in your work, please cite:                   #\n#                                                               #\n# P.A. Ravindranath S. Forli, D.S. Goodsell, A.J. Olson and     #\n# M.F. Sanner                                                   #\n# AutoDockFR: Advances in Protein-Ligand Docking with           #\n# Explicitly Specified Binding Site Flexibility                 #\n# PLoS Comput Biol 11(12): e1004586                             #\n# DOI:10.1371\/journal.pcbi.1004586                              #\n#                                                               #\n# P. Ananad Ravindranath and M.F. Sanner                        #\n# AutoSite: an automated approach for pseudoligands prediction  #\n# - From ligand binding sites identification to predicting key  #\n# ligand atoms                                                  #\n# Bioinformatics (2016)                                         #\n# DOI:10.1093\/bioinformatics\/btw367                             #\n#                                                               #\n# Please see http:\/\/adfr.scripps.edu for more information.      #\n#################################################################\n\nComputing grids on fiji a Darwin-17.7.0-x86_64-i386-64bit computer\nDate Thu Apr 18 11:43:07 2019\n\nloading receptor: data\/4EK3_rec.pdbqt\nloading ligand: data\/4EK4_lig.pdbqt\n\nset box using ligand\n    Box center:    23.332    28.922    29.598\n    Box length:    25.500    24.750    20.250\n    Box size  :        68        66        54\n    padding   :     8.000\n    spacing   :     0.375\n\nidentifying pockets using AutoSite ....\n    found 9 pocket(s)\n\n    pocket|  energy | # of |Rad. of | energy |   bns    | score  \n    number|         |points|gyration|per vol.|buriedness|v*b^2\/rg\n    ------+---------+------+--------+--------+----------+---------\n        1   -227.36   455    5.82     -0.50      0.91      65.11\n        2    -63.93    83    2.67     -0.77      0.99      30.35\n        3    -32.06    59    2.31     -0.54      0.61       9.40\n        4    -30.03    47    2.62     -0.64      0.69       8.58\n        5    -11.83    25    1.58     -0.47      0.70       7.68\n        6     -9.12    21    1.51     -0.43      0.71       7.06\n        7     -9.12    16    1.43     -0.57      0.64       4.56\n        8     -8.36    12    1.25     -0.70      0.62       3.74\n        9     -4.24    10    1.19     -0.42      0.58       2.87\n    merging clusters ...\ndone. got 728 fill Points, in 1.26 (sec)\n\nsetting map types using: ligand to ['A' 'Br' 'C' 'HD' 'N' 'NA' 'OA']\n\ncomputing maps for center=(23.332 28.922 29.598) size=(25.500 24.750 20.250) dims=(68 66 54) ...\n    711 points inside the box\n\n    maps computed in 6.95 (sec)\nthe following 14 flexible receptor atoms did not contribute to the grid calculation:\n  A:ILE10:CA,CB,CG1,CG2,CD1,\n  A:LYS33:NZ,H21,H32,H43,CA,CB,CG,CD,CE,\nAdding gradient to maps ...\nprocessing maps ... done 9.00791692734\nwriting maps ... done 1.12659287453\ndone adding gradient to maps 10.34 (sec)\nmaking target file 4EK3_rec_FR_10_33.trg ...done.\n    done. 19.17 (sec)\n<\/textarea><\/div>\n<\/div><div class=\"nav fusion-mobile-tab-nav\"><ul class=\"nav-tabs\" role=\"tablist\"><li role=\"presentation\"><a class=\"tab-link\" data-toggle=\"tab\" role=\"tab\" aria-controls=\"tab-af1607d5f15e9e0daf7\" aria-selected=\"false\" tabindex=\"-1\" id=\"mobile-fusion-tab-targetfilemeta-data\" href=\"#tab-af1607d5f15e9e0daf7\"><h4 class=\"fusion-tab-heading\"><i class=\"fontawesome-icon fa-search fas\" aria-hidden=\"true\" style=\"font-size:13px;\"><\/i>Target file meta-data<\/h4><\/a><\/li><\/ul><\/div><div class=\"tab-pane fade fusion-clearfix\" role=\"tabpanel\" tabindex=\"0\" aria-labelledby=\"fusion-tab-targetfilemeta-data\" id=\"tab-af1607d5f15e9e0daf7\">\n<h4><span style=\"color: #000000;\">Display the meta-data from a target file<\/span><\/h4>\n<style type=\"text\/css\" scopped=\"scopped\">.fusion-syntax-highlighter-6 > .CodeMirror, .fusion-syntax-highlighter-6 > .CodeMirror .CodeMirror-gutters {background-color:var(--awb-color1);}<\/style><div class=\"fusion-syntax-highlighter-container fusion-syntax-highlighter-6 fusion-syntax-highlighter-theme-light\" style=\"opacity:0;margin-top:15px;margin-right:0px;margin-bottom:15px;margin-left:0px;font-size:14px;border-width:1px;border-style:solid;border-color:var(--awb-color3);\"><div class=\"syntax-highlighter-copy-code\"><span class=\"syntax-highlighter-copy-code-title\" data-id=\"fusion_syntax_highlighter_6\" style=\"font-size:14px;\">Copy to Clipboard<\/span><\/div><label for=\"fusion_syntax_highlighter_6\" class=\"screen-reader-text\">Syntax Highlighter<\/label><textarea class=\"fusion-syntax-highlighter-textarea\" id=\"fusion_syntax_highlighter_6\" data-readOnly=\"nocursor\" data-lineNumbers=\"\" data-lineWrapping=\"\" data-theme=\"default\" data-mode=\"text\/x-sh\">about 4EK3_rec_FR_10_33.trg<\/textarea><\/div>\n<div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-separator fusion-full-width-sep\" style=\"margin-left: auto;margin-right: auto;margin-top:15px;margin-bottom:15px;width:100%;\"><div class=\"fusion-separator-border sep-double sep-solid\" style=\"--awb-height:20px;--awb-amount:20px;border-color:#e0dede;border-top-width:1px;border-bottom-width:1px;\"><\/div><\/div><div class=\"fusion-sep-clear\"><\/div>\n<p><strong>Details<\/strong>:<\/p>\n<style type=\"text\/css\" scopped=\"scopped\">.fusion-syntax-highlighter-7 > .CodeMirror, .fusion-syntax-highlighter-7 > .CodeMirror .CodeMirror-gutters {background-color:var(--awb-color1);}.fusion-syntax-highlighter-7 > .CodeMirror .CodeMirror-gutters { background-color: var(--awb-color2); }.fusion-syntax-highlighter-7 > .CodeMirror .CodeMirror-linenumber { color: var(--awb-color8); }<\/style><div class=\"fusion-syntax-highlighter-container fusion-syntax-highlighter-7 fusion-syntax-highlighter-theme-light\" style=\"opacity:0;margin-top:0px;margin-right:0px;margin-bottom:0px;margin-left:0px;font-size:14px;border-width:1px;border-style:solid;border-color:var(--awb-color3);\"><label for=\"fusion_syntax_highlighter_7\" class=\"screen-reader-text\">Syntax Highlighter<\/label><textarea class=\"fusion-syntax-highlighter-textarea\" id=\"fusion_syntax_highlighter_7\" data-readOnly=\"nocursor\" data-lineNumbers=\"1\" data-lineWrapping=\"\" data-theme=\"default\" data-mode=\"text\/x-sh\">docking target file\n  date       : Thu Apr 18 11:43:07 2019\n  node       : fiji\n  AGFR       : v1.2\n  AutoSite   : v1.0\n\n  receptor   : 4EK3_rec.pdbqt\n     FlexRec : A:ILE10,LYS33 in flexRec.pdbqt\n    covBond  : No\n\n  box        :  mode ['ligand'], padding 8.00\n    center   : 23.332 28.922 29.598\n    length   : 25.500 24.750 20.250\n    size     : 0068 0066 0054\n    spacing  : 0.375\n\n  maps       : \n    types    :  C   A   e   d  OA  Br  NA  HD   N   W \n    W map    : weight 0.60 entropy -0.20\n    gradients: Yes,  kept largest negative cluster\n\n  pocketMode : ['ligand']\n    #fillpts : 711 points\n    file     : 4EK3_rec_FR_10_33\/translationPoints.npy<\/textarea><\/div>\n<\/div><div class=\"nav fusion-mobile-tab-nav\"><ul class=\"nav-tabs\" role=\"tablist\"><li role=\"presentation\"><a class=\"tab-link\" data-toggle=\"tab\" role=\"tab\" aria-controls=\"tab-d54314ff1af0a31f795\" aria-selected=\"false\" tabindex=\"-1\" id=\"mobile-fusion-tab-dockingtheligand\" href=\"#tab-d54314ff1af0a31f795\"><h4 class=\"fusion-tab-heading\"><i class=\"fontawesome-icon fa-cogs fas\" aria-hidden=\"true\" style=\"font-size:13px;\"><\/i>Docking the ligand<\/h4><\/a><\/li><\/ul><\/div><div class=\"tab-pane fade fusion-clearfix\" role=\"tabpanel\" tabindex=\"0\" aria-labelledby=\"fusion-tab-dockingtheligand\" id=\"tab-d54314ff1af0a31f795\">\n<h4><span style=\"color: #000000;\">Perform the docking<\/span><\/h4>\n<style type=\"text\/css\" scopped=\"scopped\">.fusion-syntax-highlighter-8 > .CodeMirror, .fusion-syntax-highlighter-8 > .CodeMirror .CodeMirror-gutters {background-color:var(--awb-color1);}<\/style><div class=\"fusion-syntax-highlighter-container fusion-syntax-highlighter-8 fusion-syntax-highlighter-theme-light\" style=\"opacity:0;margin-top:0px;margin-right:0px;margin-bottom:0px;margin-left:0px;font-size:14px;border-width:1px;border-style:solid;border-color:var(--awb-color3);\"><div class=\"syntax-highlighter-copy-code\"><span class=\"syntax-highlighter-copy-code-title\" data-id=\"fusion_syntax_highlighter_8\" style=\"font-size:14px;\">Copy to Clipboard<\/span><\/div><label for=\"fusion_syntax_highlighter_8\" class=\"screen-reader-text\">Syntax Highlighter<\/label><textarea class=\"fusion-syntax-highlighter-textarea\" id=\"fusion_syntax_highlighter_8\" data-readOnly=\"nocursor\" data-lineNumbers=\"\" data-lineWrapping=\"\" data-theme=\"default\" data-mode=\"text\/x-sh\">adfr -l data\/4EK4_random.pdbqt -t 4EK3_rec_FR_10_33.trg --jobName flexRes --nbRuns 8 --maxEvals 20000 -O --seed 1<\/textarea><\/div>\n<div class=\"fusion-sep-clear\"><\/div><div class=\"fusion-separator fusion-full-width-sep\" style=\"margin-left: auto;margin-right: auto;margin-top:15px;margin-bottom:15px;width:100%;\"><div class=\"fusion-separator-border sep-double sep-solid\" style=\"--awb-height:20px;--awb-amount:20px;border-color:#e0dede;border-top-width:1px;border-bottom-width:1px;\"><\/div><\/div><div class=\"fusion-sep-clear\"><\/div>\n<p>Details: <em>ADFR<\/em>\u00a0will dock the ligand into receptor while treating the 2 side chains A:ILE10,LYS33 as flexible.\u00a0<em>adfr<\/em>\u00a0detects the number of cores available and by default will use them all to perform 8 independent searches (\u2013<span class=\"SpellE\">nbRuns<\/span>\u00a08) each using up to 20\u2019000 evaluations of the scoring function (\u2013<span class=\"SpellE\">maxEvals<\/span>\u00a02000). By default\u00a0<em>adfr<\/em>\u00a0performs 50 searches, each allotted 2.5 million evaluations. Typically, more complex docking problems require more searches to be performed to increase the chances to find the best possible docked pose (i.e. global minimum of the scoring function). Here we set these parameters to lower values to perform a quick run that is sufficient to illustrate the docking principles.<\/p>\n<p>Running this command generates the following 3 files.<\/p>\n<ul>\n<li>4EK4_random_flexRec_summary.dlg : Docking log file. captures most of the messages printed to stdout and lists additional clustering information<\/li>\n<li>4EK4_random_flexRec_out.pdbqt\u00a0 \u00a0 \u00a0 \u00a0: Multi-model pose file, listing the solutions<\/li>\n<li>4EK4_random_flexRec.dro\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0: Docking Result Object file, containing the input, output and meta-data for this docking<\/li>\n<\/ul>\n<p>NOTES:<\/p>\n<ul>\n<li>The output files are named using\u00a0the ligand name followed by the job name (\u2013<span class=\"SpellE\">jobName<\/span>\u00a0if specified)<\/li>\n<li>ADFR\u2019s search procedure is stochastic, meaning that docking the same ligand into the same target twice can produce different results if\u00a0 different random number generator seeds are used. However, the energy landscape for this receptor and ligand is the same in both runs. If both docking runs find the global minimum of this energy landscape, the solutions produced by both runs will be the same, independently of the paths taken by the search to get there. On the other hand, searches that get trapped in a local minima, yield docking poses that differ from each other. Specifying the seeds used by the random number generator (\u2013seed) allows reproducing a docking calculation, for a given version of the code.<\/li>\n<\/ul>\n<p>The output of the command is listed below:<\/p>\n<style type=\"text\/css\" scopped=\"scopped\">.fusion-syntax-highlighter-9 > .CodeMirror, .fusion-syntax-highlighter-9 > .CodeMirror .CodeMirror-gutters {background-color:var(--awb-color1);}.fusion-syntax-highlighter-9 > .CodeMirror .CodeMirror-gutters { background-color: var(--awb-color2); }.fusion-syntax-highlighter-9 > .CodeMirror .CodeMirror-linenumber { color: var(--awb-color8); }<\/style><div class=\"fusion-syntax-highlighter-container fusion-syntax-highlighter-9 fusion-syntax-highlighter-theme-light\" style=\"opacity:0;margin-top:0px;margin-right:0px;margin-bottom:0px;margin-left:0px;font-size:14px;border-width:1px;border-style:solid;border-color:var(--awb-color3);\"><label for=\"fusion_syntax_highlighter_9\" class=\"screen-reader-text\">Syntax Highlighter<\/label><textarea class=\"fusion-syntax-highlighter-textarea\" id=\"fusion_syntax_highlighter_9\" data-readOnly=\"nocursor\" data-lineNumbers=\"1\" data-lineWrapping=\"\" data-theme=\"default\" data-mode=\"text\/x-sh\">#################################################################\n# If you used ADFR in your work, please cite:                   #\n#                                                               #\n# P.A. Ravindranath S. Forli, D.S. Goodsell, A.J. Olson and     #\n# M.F. Sanner                                                   #\n#                                                               #\n# AutoDockFR: Advances in Protein-Ligand Docking with           #\n# Explicitly Specified Binding Site Flexibility                 #\n# PLoS Comput Biol 11(12): e1004586                             #\n#                                                               #\n# DOI:10.1371\/journal.pcbi.1004586                              #\n#                                                               #\n# Please see http:\/\/adfr.scripps.edu for more information.      #\n#################################################################\n\nDocking on fiji a Darwin-17.7.0-x86_64-i386-64bit computer\nDate Thu Apr 18 11:50:17 2019\nreading ligand \/Users\/sanner\/test1.1\/data\/4EK4_random.pdbqt\nDetected 4 cores, using 4 cores\nUnpacking maps \/Users\/sanner\/test1.1\/4EK3_rec_FR_10_33.trg\nPerforming search (8 GA evolutions with 20000 maxEvals each) ...\n0%   10   20   30   40   50   60   70   80   90   100%\n|----|----|----|----|----|----|----|----|----|----|\n***************************************************\nTermination status\n    0\/   8  0.0% runs failed\n    8\/   8 100.0% runs exhausted their evaluations\n    0\/   8  0.0% runs stopped converged 1 or 2 clusters\n    0\/   8  0.0% runs stopped after no improvement in clusters\n    0\/   8  0.0% runs stopped because GA ran out of choices\n    0\/   8  0.0% runs stopped because GA population converged\n\nRefining results ...\ndone.\n\nmode |  affinity  | clust. | ref. | clust. | rmsd | energy | best |\n     | (kcal\/mol) | rmsd   | rmsd |  size  | stdv |  stdv  | run  |\n-----+------------+--------+------+--------+------+--------+------+\n   1         -6.8     0.0    -1.0       4     0.7     0.4    003\n   2         -6.2     2.8    -1.0       1      NA      NA    002\n   3         -5.9     4.9    -1.0       2     0.6     0.0    007\n   4         -5.1     6.8    -1.0       1      NA      NA    008\nWriting poses to 4EK4_random_flexRes_out.pdbqt\n\nDocking performed in 8.19 seconds, i.e. 0 hours 00 minutes 08.185095 seconds \n\n*************** first GA command ***************************\n\"\/Users\/sanner\/test1.1\/mgltools2_x86_64Darwin_1.2\/bin\/pythonsh\" \"\/Users\/sanner\/test1.1\/ADFR\/bin\/runOneGA.py\" -F \"\/var\/folders\/gm\/frz8gxj57hzbyyzwtt5bq8m40000gn\/T\/tmpORGHr_\/4EK3_rec_FR_10_33\" -M rigidReceptor -R \"\/var\/folders\/gm\/frz8gxj57hzbyyzwtt5bq8m40000gn\/T\/tmpORGHr_\/4EK3_rec_FR_10_33\/4EK3_rec.pdbqt\" -X \"A:ILE10,LYS33\" -T \"\/var\/folders\/gm\/frz8gxj57hzbyyzwtt5bq8m40000gn\/T\/tmpORGHr_\/4EK3_rec_FR_10_33\/translationPoints.npy\" \"-l\" \"data\/4EK4_random.pdbqt\" \"--jobName\" \"flexRes\" \"--maxEvals\" \"20000\" \"-O\" -S 1 -j 1 -o \"4EK4_random_flexRes\/flexRes0001.dlg\"\n\npackaging docking results in to 4EK4_random_flexRes.droin  0.10 (s.)\n<\/textarea><\/div>\n<\/div><div class=\"nav fusion-mobile-tab-nav\"><ul class=\"nav-tabs\" role=\"tablist\"><li role=\"presentation\"><a class=\"tab-link\" data-toggle=\"tab\" role=\"tab\" aria-controls=\"tab-38c0c3e418cf263d8c1\" aria-selected=\"false\" tabindex=\"-1\" id=\"mobile-fusion-tab-understandingtheoutput\" href=\"#tab-38c0c3e418cf263d8c1\"><h4 class=\"fusion-tab-heading\"><i class=\"fontawesome-icon fa-lightbulb far\" aria-hidden=\"true\" style=\"font-size:13px;\"><\/i>Understanding the output<\/h4><\/a><\/li><\/ul><\/div><div class=\"tab-pane fade fusion-clearfix\" role=\"tabpanel\" tabindex=\"0\" aria-labelledby=\"fusion-tab-understandingtheoutput\" id=\"tab-38c0c3e418cf263d8c1\">\n<p>Here we describe line by line the messages output during the docking procedure.<\/p>\n<style type=\"text\/css\" scopped=\"scopped\">.fusion-syntax-highlighter-10 > .CodeMirror, .fusion-syntax-highlighter-10 > .CodeMirror .CodeMirror-gutters {background-color:var(--awb-color1);}.fusion-syntax-highlighter-10 > .CodeMirror .CodeMirror-gutters { background-color: var(--awb-color2); }.fusion-syntax-highlighter-10 > .CodeMirror .CodeMirror-linenumber { color: var(--awb-color8); }<\/style><div class=\"fusion-syntax-highlighter-container fusion-syntax-highlighter-10 fusion-syntax-highlighter-theme-light\" style=\"opacity:0;margin-top:0px;margin-right:0px;margin-bottom:15px;margin-left:0px;font-size:14px;border-width:1px;border-style:solid;border-color:var(--awb-color3);\"><label for=\"fusion_syntax_highlighter_10\" class=\"screen-reader-text\">Syntax Highlighter<\/label><textarea class=\"fusion-syntax-highlighter-textarea\" id=\"fusion_syntax_highlighter_10\" data-readOnly=\"nocursor\" data-lineNumbers=\"1\" data-lineWrapping=\"\" data-theme=\"default\" data-mode=\"text\/x-sh\">Docking on fiji a Darwin-17.7.0-x86_64-i386-64bit computer\nDate Thu Apr 18 11:50:17 2019\nreading ligand \/Users\/sanner\/test1.1\/data\/4EK4_random.pdbqt\nDetected 4 cores, using 4 cores\nUnpacking maps \/Users\/sanner\/test1.1\/4EK3_rec_FR_10_33.trg<\/textarea><\/div>\n<ol>\n<li>Hostname and platform architecture on which the program is running<\/li>\n<li>Date and time of execution<\/li>\n<li>ligand docked<\/li>\n<li>number of detected and used cores.<\/li>\n<li>target files used<\/li>\n<\/ol>\n<p>NOTES:<\/p>\n<ul>\n<li>Number of cores. By default ADFR will use all cores available to parallelize the search threads comprised in a run. Use the \u201c-c\u201d command line option to limit the number of used cores.<\/li>\n<\/ul>\n<style type=\"text\/css\" scopped=\"scopped\">.fusion-syntax-highlighter-11 > .CodeMirror, .fusion-syntax-highlighter-11 > .CodeMirror .CodeMirror-gutters {background-color:var(--awb-color1);}.fusion-syntax-highlighter-11 > .CodeMirror .CodeMirror-gutters { background-color: var(--awb-color2); }.fusion-syntax-highlighter-11 > .CodeMirror .CodeMirror-linenumber { color: var(--awb-color8); }<\/style><div class=\"fusion-syntax-highlighter-container fusion-syntax-highlighter-11 fusion-syntax-highlighter-theme-light\" style=\"opacity:0;margin-top:0px;margin-right:0px;margin-bottom:15px;margin-left:0px;font-size:14px;border-width:1px;border-style:solid;border-color:var(--awb-color3);\"><label for=\"fusion_syntax_highlighter_11\" class=\"screen-reader-text\">Syntax Highlighter<\/label><textarea class=\"fusion-syntax-highlighter-textarea\" id=\"fusion_syntax_highlighter_11\" data-readOnly=\"nocursor\" data-lineNumbers=\"1\" data-lineWrapping=\"\" data-theme=\"default\" data-mode=\"text\/x-sh\">Performing search (8 GA evolutions with 20000 maxEvals each) ...\n0%   10   20   30   40   50   60   70   80   90   100%\n|----|----|----|----|----|----|----|----|----|----|\n***************************************************\nTermination status\n    0\/   8  0.0% runs failed\n    8\/   8 100.0% runs exhausted their evaluations\n    0\/   8  0.0% runs stopped converged 1 or 2 clusters\n    0\/   8  0.0% runs stopped after no improvement in clusters\n    0\/   8  0.0% runs stopped because GA ran out of choices\n    0\/   8  0.0% runs stopped because GA population converged\n<\/textarea><\/div>\n<p>By default, ADFR performs 50 independent searches, i.e. 50 evolutions of a population of 100 individuals using a Genetic Algorithm (GA). In this example we intentionally reduced this number to 8 very short runs.<\/p>\n<p>Lines 1-4 display a progress bar indicating the percentage of these runs that completed.<\/p>\n<p>The lines below provide statistics over the termination status of these searches.\u00a0<em>ADFR<\/em>\u00a0implements several termination criteria in its search method. In this example all search terminated because they reached their maximum number of evaluations. The default number of evaluations is 2.5 millions and is usually never reached because of other termination criteria such as convergence of the population, meaning that there is no more diversity in the population and the chances to discover new solutions has become small, or the population still has diversity (i.e. it contains multiples competitive solutions) but none of these solution has improves over a user-defined number of generations (default 5).<\/p>\n<p>Typically, you want searches to end because the population converged or there was no improvement. A result like the one shown here is a clear indication that this docking problem needs more evaluations per search (i.e. increased \u2013maxEvals).<\/p>\n<p>The next section lists the results:<\/p>\n<style type=\"text\/css\" scopped=\"scopped\">.fusion-syntax-highlighter-12 > .CodeMirror, .fusion-syntax-highlighter-12 > .CodeMirror .CodeMirror-gutters {background-color:var(--awb-color1);}.fusion-syntax-highlighter-12 > .CodeMirror .CodeMirror-gutters { background-color: var(--awb-color2); }.fusion-syntax-highlighter-12 > .CodeMirror .CodeMirror-linenumber { color: var(--awb-color8); }<\/style><div class=\"fusion-syntax-highlighter-container fusion-syntax-highlighter-12 fusion-syntax-highlighter-theme-light\" style=\"opacity:0;margin-top:0px;margin-right:0px;margin-bottom:0px;margin-left:0px;font-size:14px;border-width:1px;border-style:solid;border-color:var(--awb-color3);\"><label for=\"fusion_syntax_highlighter_12\" class=\"screen-reader-text\">Syntax Highlighter<\/label><textarea class=\"fusion-syntax-highlighter-textarea\" id=\"fusion_syntax_highlighter_12\" data-readOnly=\"nocursor\" data-lineNumbers=\"1\" data-lineWrapping=\"\" data-theme=\"default\" data-mode=\"text\/x-sh\">mode |  affinity  | clust. | ref. | clust. | rmsd | energy | best |\n     | (kcal\/mol) | rmsd   | rmsd |  size  | stdv |  stdv  | run  |\n-----+------------+--------+------+--------+------+--------+------+\n   1         -6.8     0.0    -1.0       4     0.7     0.4    003\n   2         -6.2     2.8    -1.0       1      NA      NA    002\n   3         -5.9     4.9    -1.0       2     0.6     0.0    007\n   4         -5.1     6.8    -1.0       1      NA      NA    008\n<\/textarea><\/div>\n<p>In this docking run, the 8 searches lead to 4 distinct solutions, listed in the result table above. The solutions are sorted by descending predicted affinity. The top ranking solution was identified by 4 of the 8 searches (<em>clust. size<\/em>\u00a0column) and the pose with the best affinity was found by search number 3 (<em>best run <\/em>column). The second best solution was found 1 time and has an RMSD of 2.8 Angstroms with the top ranking solution (<em>clust. rmsd<\/em>\u00a0column). If a reference ligand pose had been specified (-r\/reference option), The\u00a0<em>ref. rmsd<\/em>\u00a0column would list the RMSD between the docked pose and the reference structure instead of listing -1.<\/p>\n<p>NOTE: RMSD values are calculated using all isomorphisms\u00a0 between the 2 molecules, thus matching symmetry related atoms and providing a more accurate measure that used in\u00a0<em>AutoDock4<\/em>,\u00a0<em>Vina<\/em>, and previous versions of\u00a0<em>AutoDockFR<\/em>.<\/p>\n<\/div><\/div><\/div><div class=\"fusion-clearfix\"><\/div><\/div><\/div><\/div><\/div>\n","protected":false},"excerpt":{"rendered":"<p>This page was last updated on October 30th, 2019 at  [&#8230;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-883","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/ccsb.scripps.edu\/adfr\/wp-json\/wp\/v2\/pages\/883","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ccsb.scripps.edu\/adfr\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/ccsb.scripps.edu\/adfr\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/ccsb.scripps.edu\/adfr\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/ccsb.scripps.edu\/adfr\/wp-json\/wp\/v2\/comments?post=883"}],"version-history":[{"count":20,"href":"https:\/\/ccsb.scripps.edu\/adfr\/wp-json\/wp\/v2\/pages\/883\/revisions"}],"predecessor-version":[{"id":1125,"href":"https:\/\/ccsb.scripps.edu\/adfr\/wp-json\/wp\/v2\/pages\/883\/revisions\/1125"}],"wp:attachment":[{"href":"https:\/\/ccsb.scripps.edu\/adfr\/wp-json\/wp\/v2\/media?parent=883"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}