Supplementary MaterialsS1 Fig: POP structure. cleavage of the fragments that are assumed P1PF. purchase BSF 208075 Comparable fragments are connected by colored boxes.(TIF) pcbi.1007713.s002.tif (93K) GUID:?7C0DF102-DA8B-4565-B74C-1D2EDC6F4506 S3 Fig: A matrix of Tanimoto values between the cP52 set (the names of the source PDB are in the upper line) and the ncP52 set (the names of the ChEMBL sources are in the left column). As the Tanimoto value is higher, the number appears more Rabbit polyclonal to TGFB2 black than gray. The maximum Tanimoto value is calculated for each molecule, last column (as the maximum value is higher, the number is marked in deeper purchase BSF 208075 blue). Four fragments are identical in these two sets.(TIF) pcbi.1007713.s003.tif (166K) GUID:?B4C74BC3-5D19-4442-B344-590A62392FD2 S4 Fig: Distinguishing between ncP52 and other sets by the ISE model. A) ROC curve of the ISE model (ncP52 vs. random molecules). B) The same curve replacing ncP52 fragments by the original inhibitors. The difference in AUC is usually huge (0.97 vs. 0.59) and indicates randomness of the results for the original inhibitors as True positives, while there is confidence in the results for the ncP52 fragments as True positives.(TIF) pcbi.1007713.s004.tif (75K) GUID:?BB4B7F39-9C54-48DF-9A62-478CCA4E5957 S5 Fig: Groups of molecules sent for in vitro tests from left to right: A) Top pharmacophore candidates (2); B) Other pharmacophore candidates (6); C) Top ISE candidates (8); D) Other ISE candidates (4); E) Tanimoto only candidates with minimal MBI (3) F) Random molecules from Enamine (2).(TIFF) pcbi.1007713.s005.tiff (9.8K) GUID:?B5D8BC72-95F2-416A-AC92-08FCBB154F2A S6 Fig: Reversed phase high pressure liquid chromatography (RP-HPLC) of Ang III and TRH peptides. Chromatograms (Absorption at 214 nm plotted against time) obtained by analyzing the reaction mixture of rhPOP and Ang III or TRH by RP-HPLC are shown. A) Chromatogram of the reaction mixture of rhPOP and Ang III. B) Chromatogram of the reaction mixture of rhPOP and TRH.(TIF) pcbi.1007713.s006.tif (59K) GUID:?C570AC0A-99F6-45A1-A42A-7E25058559C9 S7 Fig: MALDI-TOF MS spectra of TRH (pGlu-His-Pro-NH2: 362.39 g/mol) at retention time 14.8 min (upper), and TRH-OH (pGlu-His-Pro-OH: 363.67 g/mol) at retention time 17.0 min (lower).(TIF) pcbi.1007713.s007.tif (221K) GUID:?0314C1DD-0B80-4405-928B-AEBC86DAF8BF S8 Fig: Measurements of IC50 values (for activity of Ang-III and TRH) in the presence of T6816369 and T5450157. (TIF) pcbi.1007713.s008.tif (74K) GUID:?30104386-960B-45F9-827B-F1B4EFA83E89 S1 Table: 15 complexes of POP-inhibitors. The organism source is indicated, as well as the purchase BSF 208075 RMSD with respect to 1E8N.(PDF) pcbi.1007713.s009.pdf (245K) GUID:?1DA94E00-DD1A-414F-AFBE-B9B395D9FDF6 S2 Table: Applicability domain name calculation for choosing the set of inactives. Applicability domain name is required in order to avoid the inclusion of learning set molecules that have very different properties than the “actives” (such as salt or huge molecules) and might therefore bias the modeling. Calculations are based upon the 174 active molecules from ChEMBL. For each of the descriptors representing Lipinski’s rule of five the average and the standard deviations () are calculated for the “actives”. Random molecules must have the 4 properties within the range of the average plus/minus 2 standard deviations.(PDF) pcbi.1007713.s010.pdf (342K) GUID:?6B896C82-1D29-4A4C-A9B9-6BD5977AD3B7 S3 Table: Coordinates of the features in the pharmacophore model. purchase BSF 208075 (PDF) pcbi.1007713.s011.pdf (279K) GUID:?AFCD3226-4195-42CE-8DE5-348354EEF21F S4 Table: Number of molecules that passed the Pharmacophore test for each set, according to the different approaches. Lines are for the different sets of molecules, columns are for the different pharmacophore methods. In the case of the “Visual Inspection” strategy we specify whether there are more than 15 or more than 30. The last columns present the “consensus”the number of molecules successful in each method and the number of molecules in the set.(PDF) pcbi.1007713.s012.pdf (179K) GUID:?56C72707-940F-4E8B-A4F3-7FBD878F76E4 S5 Table: Detailed presentation for each molecule that passed one of the strategies and the overlap rate between the strategies. The molecules are sorted according to the percentage of the desirable conformations out of all the conformations that are supplied by the program in the “Visual Inspection” strategy. The last column shows if the molecule succeeded or not according to all the approaches.(PDF) pcbi.1007713.s013.pdf (228K) GUID:?788DF5BD-0842-4B3A-9C16-EC2AC00007FB S6 Table: Number of molecules from different sets that are above the ISE MBI cutoff. Columns, left to right: Cutoffs of MBI; ncP52 fragments; ChEMBL inhibitors; random molecules from the learning set (ncRandom); unique cP52 fragments (cP52); X-ray inhibitors; Random molecules from the external test set (cRandom); and initial candidate SSIs.(PDF) pcbi.1007713.s014.pdf (193K) GUID:?DDAA6AFC-DA1F-4221-A1D9-2B6DEF3229C8 S7 Table: MBI values of.