G-protein based reshaping

PREDICTION.md

@@ -0,0 +1,69 @@
+
+# Predicting Receptor Responses to Ligands
+
+At this time, no method yet exists to accurately identify agonist and non-agonist ligands from PrimaryDock output.
+To the best of our knowledge, either no one has developed this capability, or they have not released it to the public.
+Nevertheless, we continue to strive towards accurate predictions of GPCR agonism by odorants.
+
+# Prediction Methods
+
+PrimaryDock prediction methods are cronnable PHP scripts that perform docks of known ligands in PDB files and aggregate
+the resulting data into a JSON file. A prediction method begins with `require("methods_common.php");`, followed by a
+call to `prepare_outputs();` which generates the output file names as well as some other custom variables. A string
+value named `$configf` is then set, containing the config file to be generated for the `primarydock` app, and then the
+`process_dock()` function is called.
+
+The most current prediction method is `method_coupled.php`. To use this prediction method, one must first generate PDBs
+of all the olfactory GPCRs coupled to G proteins. This is handled by another cronnable PHP script named
+`generate_couple.php`. Here's an example crontab:
+
+```
+* * * * * php -f /path/to/primarydock/predict/generate_couple.php next
+* * * * * php -f /path/to/primarydock/predict/method_coupled.php next simul=4
+```
+
+The prediction method will not begin processing until no more instances of `generate_couple.php` are running. For both
+scripts, the `next` parameter means find the next GPCR/G-protein pair or GPCR/ligand pair yet to process, and process
+it. For `generate_couple.php`, the next pair to process is the first combination of GPCR/G-protein that does not yet
+have a PDB file in the `pdbs/coupled/` folder. For `method_coupled.php`, the next pair to process is the first pair of
+GPCR + known ligand (whether agonist or not) that either is not present in `predict/dock_results_coupled.json` or has
+a `version` value older than either the prediction method PHP, `methods_common.php`, or the `/bin/primarydock`
+executable.
+
+The `simul=4` parameter indicates not to run more than 4 concurrent processes. We recommend a value of half the number
+of cores on your machine, so if you have a server with one 8-core processor, then `simul=4` would be the recommended
+value, whereas if you are running it on a 4-core machine, then we recommend `simul=2` instead.
+
+You can use the `predict/progress.sh` shell script to monitor the cron's progress.
+
+# Writing Your Own Prediction Methods
+
+Until an accurate prediction method exists, we encourage you to write your own prediction methods. You can use the
+`method_basic.php` script as a template, and then apply any variations you wish. If you create a method that makes
+predictions with at least 80% accuracy, we'd be delighted to accept your pull request.
+
+Configurable variables include:
+`$dock_metals`          If true, the dock will use PDBs that end in `.metal.pdb` instead of the default `.upright.pdb`.
+                        You probably won't ever have to use the `$dock_metals` feature.
+`$dock_retries`         The number of times to retry if no poses returned. Each retry increases the energy limit.
+                        Default = 5.
+`$bias_by_energy`       TODO: This has not been implemented yet.
+`$metrics_to_process`   An array of key-value pairs identifying a dock metric and its new key in the output JSON.
+                        Valid keys can be found in the table below; the value becomes the metric's key in the JSON.
+
+Available parameters for `$metrics_to_process` include:
+`BENERG`                Total binding energy between ligand and protein;
+`BENERG.rgn`            Total binding energy between ligand and specific regions of the protein, e.g. TMR6;
+`vdWRPL`                Total van der Waals repulsion (i.e. where atoms are < 4Å apart) ligand to protein;
+`vdWRPL.rgn`            Total vdW repulsion between ligand and regions of protein;
+`POLSAT`                Ligand's sum polar satisfaction, a measure of polar-polar and nonpolar-nonpolar proximity;
+`PCLASH`                Clashes between residues of the protein, minus clashes in the original PDB model;
+
+`ACVTH.TMR1` thru `ACVTH.TMR7`
+                        Angles of helix rotations performed for a "soft dock", in which the helices are allowed to move.
+
+`POSES`                 Total number of poses found.
+`CALOC.rgn`             Average relative motion of alpha carbon atoms within each region as a result of a "soft dock".
+
+For keys ending with `.rgn`, the `rgn` will be replaced with the actual region name. For example, if the method PHP
+specifies `BENERG.rgn` => `energy.rgn`, then the JSON will contain metrics labeled `energy.TMR3`, `energy.TMR6`, etc.

data/aminos.dat

@@ -35,4 +35,3 @@ W		Trp		tryptophan			N[C@H](C(=O)O)CC1=CNc2ccccc21                            -
 Y		Tyr		tyrosine			N[C@H](C(=O)O)Cc1ccc(O)cc1                              10.46             .071
 V		Val		valine				N[C@H](C(=O)O)C(C)C                                      -                .080
 
-

data/gprots_aligned.txt

@@ -0,0 +1,18 @@
+
+# Conserved         MG                  C L             S        EEK         IEKQL  D        KLLLLGAGESGKST VKQMKIIH  GYS E          SNT Q                                                                          LW D GIQ CF RSREYQL DSA YYLNQLDRI    Y PTQQDVL  RV TTGIIE  F      FRM DVGGQRSERKKWIHCFE VTCIIFCVALS YD  L E        ES  LF SI    FF   SIILFLNK DL  EKI          FPEY               YI             K  I                YS  H TCATDTQNIQFVF     D IIQN NLK  
+hGNAO1              MG------------------CTL-------------S-------AEERAALERSKA-IEKNLKEDGISAAKDVKLLLLGAGESGKSTIVKQMKIIHEDGFSGEDVKQYKPVVYSNTIQSLAAIVRAMDTLG------IEYGDKERKADAKMVCDVVSRMEDTEPFSAELLSA-----------------MMRLWGDSGIQECFNRSREYQLNDSAKYYLDSLDRIGAADYQPTEQDILRTRVKTTGIVETHFTFKNLHFRLFDVGGQRSERKKWIHCFEDVTAIIFCVALSGYDQVLHEDETTNRMHESLMLFDSICNNKFFIDTSIILFLNKKDLFGEKI--KKSPLTICFPEYTGPNTYE----DAAAYIQAQFESKNRSP-NKE-I----------------YC--HMTCATDTNNIQVVF-DAVTDIIIAN-NLR--GCGLY
+hGNAI1              MG------------------CTL-------------S-------AEDKAAVERSKM-IDRNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEAGYSEEECKQYKAVVYSNTIQSIIAIIRAMGRLK------IDFGDSARADDARQLFVLAGAAEEGFMTA-ELAGV-----------------IKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVKTTGIVETHFTFKDLHFKMFDVGGQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEMNRMHESMKLFDSICNNKWFTDTSIILFLNKKDLFEEKI--KKSPLTICYPEYAGSNTYE----EAAAYIQCQFEDLNKRKDTKE-I----------------YT--HFTCATDTKNVQFVF-DAVTDVIIKN-NLK--DCGLF
+hGNAI2              MG------------------CTV-------------S-------AEDKAAAERSKM-IDKNLREDGEKAAREVKLLLLGAGESGKSTIVKQMKIIHEDGYSEEECRQYRAVVYSNTIQSIMAIVKAMGNLQ------IDFADPSRADDARQLFALSCTAEEQGVLPDDLSGV-----------------IRRLWADHGVQACFGRSREYQLNDSAAYYLNDLERIAQSDYIPTQQDVLRTRVKTTGIVETHFTFKDLHFKMFDVGGQRSERKKWIHCFEGVTAIIFCVALSAYDLVLAEDEEMNRMHESMKLFDSICNNKWFTDTSIILFLNKKDLFEEKI--THSPLTICFPEYTGANKYD----EAASYIQSKFEDLNKRKDTKE-I----------------YT--HFTCATDTKNVQFVF-DAVTDVIIKN-NLK--DCGLF
+hGNAI3              MG------------------CTL-------------S-------AEDKAAVERSKM-IDRNLREDGEKAAKEVKLLLLGAGESGKSTIVKQMKIIHEDGYSEDECKQYKVVVYSNTIQSIIAIIRAMGRLK------IDFGEAARADDARQLFVLAGSAEEGVMTP-ELAGV-----------------IKRLWRDGGVQACFSRSREYQLNDSASYYLNDLDRISQSNYIPTQQDVLRTRVKTTGIVETHFTFKDLYFKMFDVGGQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEMNRMHESMKLFDSICNNKWFTETSIILFLNKKDLFEEKI--KRSPLTICYPEYTGSNTYE----EAAAYIQCQFEDLNRRKDTKE-I----------------YT--HFTCATDTKNVQFVF-DAVTDVIIKN-NLK--ECGLY
+hGNAT1              MG------------------AGA-------------S-------AEEK----HSRE-LEKKLKEDAEKDARTVKLLLLGAGESGKSTIVKQMKIIHQDGYSLEECLEFIAIIYGNTLQSILAIVRAMTTLN------IQYGDSARQDDARKLMHMADTIEEGTMPK-EMSDI-----------------IQRLWKDSGIQACFERASEYQLNDSAGYYLSDLERLVTPGYVPTEQDVLRSRVKTTGIIETQFSFKDLNFRMFDVGGQRSERKKWIHCFEGVTCIIFIAALSAYDMVLVEDDEVNRMHESLHLFNSICNHRYFATTSIVLFLNKKDVFFEKI--KKAHLSICFPDYDGPNTYE----DAGNYIKVQFLELNMRRDVKE-I----------------YS--HMTCATDTQNVKFVF-DAVTDIIIKE-NLK--DCGLF
+hGNAT2              MG------------------SGA-------------S-------AEDKELAKRSKE-LEKKLQEDADKEAKTVKLLLLGAGESGKSTIVKQMKIIHQDGYSPEECLEFKAIIYGNVLQSILAIIRAMTTLG------IDYAEPSCADDGRQLNNLADSIEEGTMPP-ELVEV-----------------IRRLWKDGGVQACFERAAEYQLNDSASYYLNQLERITDPEYLPSEQDVLRSRVKTTGIIETKFSVKDLNFRMFDVGGQRSERKKWIHCFEGVTCIIFCAALSAYDMVLVEDDEVNRMHESLHLFNSICNHKFFAATSIVLFLNKKDLFEEKI--KKVHLSICFPEYDGNNSYD----DAGNYIKSQFLDLNMRKDVKE-I----------------YS--HMTCATDTQNVKFVF-DAVTDIIIKE-NLK--DCGLF
+hGNAT3              MG------------------SGI-------------S-------SESKESAKRSKE-LEKKLQEDAERDARTVKLLLLGAGESGKSTIVKQMKIIHKNGYSEQECMEFKAVIYSNTLQSILAIVKAMTTLG------IDYVNPRSAEDQRQLYAMANTLEDGGMTP-QLAEV-----------------IKRLWRDPGIQACFERASEYQLNDSAAYYLNDLDRITASGYVPNEQDVLHSRVKTTGIIETQFSFKDLHFRMFDVGGQRSERKKWIHCFEGVTCIIFCAALSAYDMVLVEDEEVNRMHESLHLFNSICNHKYFSTTSIVLFLNKKDIFQEKV--TKVHLSICFPEYTGPNTFE----DAGNYIKNQFLDLNLKKEDKE-I----------------YS--HMTCATDTQNVKFVF-DAVTDIIIKE-NLK--DCGLF
+hGNAZ               MG------------------CRQ-------------S-------SEEKEAARRSRR-IDRHLRSESQRQRREIKLLLLGTSNSGKSTIVKQMKIIHSGGFNLEACKEYKPLIIYNAIDSLTRIIRALAALR------IDFHNPDRAYDAVQLFALTGPAESKGEITPELLGV-----------------MRRLWADPGAQACFSRSSEYHLEDNAAYYLNDLERIAAADYIPTVEDILRSRDMTTGIVENKFTFKELTFKMVDVGGQRSERKKWIHCFEGVTAIIFCVELSGYDLKLYEDNQTSRMAESLRLFDSICNNNWFINTSLILFLNKKDLLAEKI--RRIPLTICFPEYKGQNTYE----EAAVYIQRQFEDLNRNKETKE-I----------------YS--HFTCATDTSNIQFVF-DAVTDVIIQN-NLK-Y-IGLC
+hGNAS2              MG------------------CLG------------NSKT-EDQRNEEKAQREANKK-IEKQLQKDKQVYRATHRLLLLGAGESGKSTIVKQMRILHVNGFNGEGGEEDPQAARSNSDGEKAT--KVQDI-KNNLKEAIETIVAAMSNLVPP-VELANPENQFRVDYILSVMNVPD--FDFP--PEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLDKIDVIKQADYVPSDQDLLRCRVLTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVASSSYNMVIREDNQTNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPE----DAT---PEPGEDP-RVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENIRRVFNDC-RD-IIQRMHLRQYEL-L-
+hGNAL               MG------------------CLGG-----------NSKTTEDQGVDEKERREANKK-IEKQLQKERLAYKATHRLLLLGAGESGKSTIVKQMRILHVNGFNP---EEKKQ--------------KILDI-RKNVKDAIVTIVSAMSTIIPP-VPLANPENQFRSDYIKSIAPITD--FEYS--QEFFDHVKKLWDDEGVKACFERSNEYQLIDCAQYFLERIDSVSLVDYTPTDQDLLRCRVLTSGIFETRFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIYVAACSSYNMVIREDNNTNRLRESLDLFESIWNNRWLRTISIILFLNKQDMLAEKVLAGKSKIEDYFPEYANYTVPE----DAT---PDAGEDP-KVTRAKFFIRDLFLRISTATGDGKHYCYPHFTCAVDTENIRRVFNDC-RD-IIQRMHLKQYEL-L-
+hGNAQ               M------------TLESIMACCL---------------------SEEAKEARRINDEIERQLRRDKRDARRELKLLLLGTGESGKSTFIKQMRIIHGSGYS-D--EDKRG------------FTKLVY--QNIFTAMQAMIRAMDTLKIPYKYEHNKAHAQLVREVDVEKVSA----FENP----YVDAIKSLWNDPGIQECYDRRREYQLSDSTKYYLNDLDRVADPAYLPTQQDVLRVRVPTTGIIEYPFDLQSVIFRMVDVGGQRSERRKWIHCFENVTSIMFLVALSEYDQVLVESDNENRMEESKALFRTIITYPWFQNSSVILFLNKKDLLEEKIM--YSHLVDYFPEY-D--GPQRDAQAAREFILKMFVDLNPDSD-KI-I----------------YS--HFTCATDTENIRFVFA-AVKDTILQL-NLKEYNL-V-
+hGNA11              M------------TLESMMACCL---------------------SDEVKESKRINAEIEKQLRRDKRDARRELKLLLLGTGESGKSTFIKQMRIIHGAGYS-E--EDKRG------------FTKLVY--QNIFTAMQAMIRAMETLKILYKYEQNKANALLIREVDVEKVTT----FEHQ----YVSAIKTLWEDPGIQECYDRRREYQLSDSAKYYLTDVDRIATLGYLPTQQDVLRVRVPTTGIIEYPFDLENIIFRMVDVGGQRSERRKWIHCFENVTSIMFLVALSEYDQVLVESDNENRMEESKALFRTIITYPWFQNSSVILFLNKKDLLEDKIL--YSHLVDYFPEF-D--GPQRDAQAAREFILKMFVDLNPDSD-KI-I----------------YS--HFTCATDTENIRFVFA-AVKDTILQL-NLKEYNL-V-
+hGNA12              MSGVVRTLSR----------CLLPAEAGGARERRAGSGA-----RDAEREARRRSRDIDALLARERRAVRRLVKILLLGAGESGKSTFLKQMRIIHGR----E--FDQKALL---------EFRDTIF--DNILKGSRVLVDARDKLGIPWQYSENEKHGMFLMAFENKAGLP----VEPATFQLYVPALSALWRDSGIREAFSRRSEFQLGESVKYFLDNLDRIGQLNYFPSKQDILLARKATKGIVEHDFVIKKIPFKMVDVGGQRSQRQKWFQCFDGITSILFMVSSSEYDQVLMEDRRTNRLVESMNIFETIVNNKLFFNVSIILFLNKMDLLVEKVKT-VSIKK-HFPDFR---GDPHRLEDVQRYLVQCFDRKRRNRS-KP-L----------------FH--HFTTAIDTENVRFVFH-AVKDTILQE-NLKDIML-Q-
+hGNA13              MAD---FLPSRSVLSVCFPGCLLTS---------------------GEAEQQRKSKEIDKCLSREKTYVKRLVKILLLGAGESGKSTFLKQMRIIHGQ----D--FDQRAR---------EEFRPTIY--SNVIKGMRVLVDAREKLHIPWGDNSNQQHGDKMMSFDTRAPMAAQGMVETRVFLQYLPAIRALWADSGIQNAYDRRREFQLGESVKYFLDNLDKLGEPDYIPSQQDILLARRPTKGIHEYDFEIKNVPFKMVDVGGQRSERKRWFECFDSVTSILFLVSSSEFDQVLMEDRLTNRLTESLNIFETIVNNRVFSNVSIILFLNKTDLLEEKVQI-VSIKD-YFLEFE---GDPHCLRDVQKFLVECFRNKRRDQQQKP-L----------------YH--HFTTAINTENIRLVFR-DVKDTILHD-NLKQLML-Q-
+hGNA14              MAG-----------------CCCL--------------------SAEEKESQRISAEIERQLRRDKKDARRELKLLLLGTGESGKSTFIKQMRIIHGSGYS-D--EDRKGFTKLVYQNIFTAMQAMIRAMDTLRIQYVCEQNKENAQIIREVEVDKVSMLSREQVE----------------------AIKQLWQDPGIQECYDRRREYQLSDSAKYYLTDIDRIATPSFVPTQQDVLRVRVPTTGIIEYPFDLENIIFRMVDVGGQRSERRKWIHCFESVTSIIFLVALSEYDQVLAECDNENRMEESKALFKTIITYPWFLNSSVILFLNKKDLLEEKIMY--SHLISYFPEYT---GPKQDVRAARDFILKLYQDQNPDKE-KV-I----------------YS--HFTCATDTDNIRFVFA-AVKDTILQL-NLREFNL-V-
+