J Chem Inf Model - Combining horizontal and vertical substructure relationships in scaffold hierarchies for activity prediction.

Tópicos

{ compound(1573) activ(1297) structur(1058) }
{ structur(1116) can(940) graph(676) }
{ data(1737) use(1416) pattern(1282) }
{ cost(1906) reduc(1198) effect(832) }
{ perform(999) metric(946) measur(919) }
{ model(2341) predict(2261) use(1141) }
{ perform(1367) use(1326) method(1137) }
{ studi(1119) effect(1106) posit(819) }
{ signal(2180) analysi(812) frequenc(800) }
{ patient(1821) servic(1111) care(1106) }
{ featur(3375) classif(2383) classifi(1994) }
{ take(945) account(800) differ(722) }
{ framework(1458) process(801) describ(734) }
{ error(1145) method(1030) estim(1020) }
{ learn(2355) train(1041) set(1003) }
{ extract(1171) text(1153) clinic(932) }
{ design(1359) user(1324) use(1319) }
{ data(3963) clinic(1234) research(1004) }
{ visual(1396) interact(850) tool(830) }
{ model(2656) set(1616) predict(1553) }
{ group(2977) signific(1463) compar(1072) }
{ data(3008) multipl(1320) sourc(1022) }
{ high(1669) rate(1365) level(1280) }
{ drug(1928) target(777) effect(648) }
{ model(3404) distribut(989) bayesian(671) }
{ can(774) often(719) complex(702) }
{ imag(1947) propos(1133) code(1026) }
{ inform(2794) health(2639) internet(1427) }
{ system(1976) rule(880) can(841) }
{ measur(2081) correl(1212) valu(896) }
{ imag(1057) registr(996) error(939) }
{ bind(1733) structur(1185) ligand(1036) }
{ sequenc(1873) structur(1644) protein(1328) }
{ method(1219) similar(1157) match(930) }
{ imag(2830) propos(1344) filter(1198) }
{ network(2748) neural(1063) input(814) }
{ imag(2675) segment(2577) method(1081) }
{ patient(2315) diseas(1263) diabet(1191) }
{ studi(2440) review(1878) systemat(933) }
{ motion(1329) object(1292) video(1091) }
{ assess(1506) score(1403) qualiti(1306) }
{ treatment(1704) effect(941) patient(846) }
{ surgeri(1148) surgic(1085) robot(1054) }
{ problem(2511) optim(1539) algorithm(950) }
{ chang(1828) time(1643) increas(1301) }
{ concept(1167) ontolog(924) domain(897) }
{ clinic(1479) use(1117) guidelin(835) }
{ algorithm(1844) comput(1787) effici(935) }
{ method(1557) propos(1049) approach(1037) }
{ data(1714) softwar(1251) tool(1186) }
{ control(1307) perform(991) simul(935) }
{ model(2220) cell(1177) simul(1124) }
{ care(1570) inform(1187) nurs(1089) }
{ general(901) number(790) one(736) }
{ method(984) reconstruct(947) comput(926) }
{ search(2224) databas(1162) retriev(909) }
{ featur(1941) imag(1645) propos(1176) }
{ case(1353) use(1143) diagnosi(1136) }
{ howev(809) still(633) remain(590) }
{ studi(1410) differ(1259) use(1210) }
{ risk(3053) factor(974) diseas(938) }
{ research(1085) discuss(1038) issu(1018) }
{ system(1050) medic(1026) inform(1018) }
{ import(1318) role(1303) understand(862) }
{ blood(1257) pressur(1144) flow(957) }
{ spatial(1525) area(1432) region(1030) }
{ record(1888) medic(1808) patient(1693) }
{ health(3367) inform(1360) care(1135) }
{ model(3480) simul(1196) paramet(876) }
{ monitor(1329) mobil(1314) devic(1160) }
{ ehr(2073) health(1662) electron(1139) }
{ state(1844) use(1261) util(961) }
{ research(1218) medic(880) student(794) }
{ patient(2837) hospit(1953) medic(668) }
{ data(2317) use(1299) case(1017) }
{ age(1611) year(1155) adult(843) }
{ medic(1828) order(1363) alert(1069) }
{ sampl(1606) size(1419) use(1276) }
{ gene(2352) biolog(1181) express(1162) }
{ first(2504) two(1366) second(1323) }
{ intervent(3218) particip(2042) group(1664) }
{ activ(1138) subject(705) human(624) }
{ time(1939) patient(1703) rate(768) }
{ use(2086) technolog(871) perceiv(783) }
{ can(981) present(881) function(850) }
{ analysi(2126) use(1163) compon(1037) }
{ health(1844) social(1437) communiti(874) }
{ cancer(2502) breast(956) screen(824) }
{ use(976) code(926) identifi(902) }
{ use(1733) differ(960) four(931) }
{ result(1111) use(1088) new(759) }
{ implement(1333) system(1263) develop(1122) }
{ survey(1388) particip(1329) question(1065) }
{ estim(2440) model(1874) function(577) }
{ decis(3086) make(1611) patient(1517) }
{ process(1125) use(805) approach(778) }
{ activ(1452) weight(1219) physic(1104) }
{ method(1969) cluster(1462) data(1082) }
{ method(2212) result(1239) propos(1039) }
{ detect(2391) sensit(1101) algorithm(908) }

Resumo

For a systematic exploration of structural relationships between molecular scaffolds, ~24,000 unique scaffolds were extracted from 458 different target sets. Substructure relationships between these scaffolds were systematically determined. The scaffold tree data structure was utilized to study structural relationships between original scaffolds and derivative scaffolds obtained by rule-based decomposition. Leaf-to-root substructure relationships that resulted from rule-based decomposition were compared to leaf-to-leaf relationships between original scaffolds most of which were not part of the scaffold tree hierarchy. Decomposed scaffolds not contained in active target set compounds were prioritized on the basis of hierarchical scaffold patterns and additional substructure relationships. For high-priority virtual scaffolds, activity predictions were carried out, and these scaffolds were often found in external test compounds having the predicted activity. Taken together, our results suggest that leaf-to-root substructure relationships in scaffold trees should best be complemented with additional substructure relationships to determine high-priority virtual scaffolds for activity prediction.

Resumo Limpo

systemat explor structur relationship molecular scaffold uniqu scaffold extract differ target set substructur relationship scaffold systemat determin scaffold tree data structur util studi structur relationship origin scaffold deriv scaffold obtain rulebas decomposit leaftoroot substructur relationship result rulebas decomposit compar leaftoleaf relationship origin scaffold part scaffold tree hierarchi decompos scaffold contain activ target set compound priorit basi hierarch scaffold pattern addit substructur relationship highprior virtual scaffold activ predict carri scaffold often found extern test compound predict activ taken togeth result suggest leaftoroot substructur relationship scaffold tree best complement addit substructur relationship determin highprior virtual scaffold activ predict

Resumos Similares

J Chem Inf Model - Polypharmacology directed compound data mining: identification of promiscuous chemotypes with different activity profiles and comparison to approved drugs. ( 0,964414469731684 )
J Chem Inf Model - Locating sweet spots for screening hits and evaluating pan-assay interference filters from the performance analysis of two lead-like libraries. ( 0,944031701442627 )
J Chem Inf Model - TIN-a combinatorial compound collection of synthetically feasible multicomponent synthesis products. ( 0,942646510159187 )
J Chem Inf Model - Natural product-like virtual libraries: recursive atom-based enumeration. ( 0,939860785196191 )
J Chem Inf Model - In silico enzymatic synthesis of a 400,000 compound biochemical database for nontargeted metabolomics. ( 0,936818250742085 )
J Chem Inf Model - G-protein coupled receptors virtual screening using genetic algorithm focused chemical space. ( 0,934282011871207 )
J Chem Inf Model - Target-independent prediction of drug synergies using only drug lipophilicity. ( 0,931561110498205 )
J Chem Inf Model - Identification of 1,2,5-oxadiazoles as a new class of SENP2 inhibitors using structure based virtual screening. ( 0,930322384675904 )
Curr Comput Aided Drug Des - Development of Chemical Compound Libraries for In Silico Drug Screening. ( 0,928186672184786 )
J Chem Inf Model - Automated recycling of chemistry for virtual screening and library design. ( 0,92750998108032 )
J Chem Inf Model - From activity cliffs to activity ridges: informative data structures for SAR analysis. ( 0,927372109019636 )
J Chem Inf Model - Increasing the coverage of medicinal chemistry-relevant space in commercial fragments screening. ( 0,926485207833059 )
J Chem Inf Model - Design of multitarget activity landscapes that capture hierarchical activity cliff distributions. ( 0,925952226900611 )
J Chem Inf Model - Compound optimization through data set-dependent chemical transformations. ( 0,925702819639487 )
J Chem Inf Model - Identification of multitarget activity ridges in high-dimensional bioactivity spaces. ( 0,923899241814584 )
J Chem Inf Model - QSAR classification model for antibacterial compounds and its use in virtual screening. ( 0,92173934645711 )
J Chem Inf Model - Prediction of individual compounds forming activity cliffs using emerging chemical patterns. ( 0,921727435131461 )
J Chem Inf Model - Identifying compound-target associations by combining bioactivity profile similarity search and public databases mining. ( 0,921350089131282 )
J Chem Inf Model - Compound set enrichment: a novel approach to analysis of primary HTS data. ( 0,921206566780803 )
J Chem Inf Model - Design of a three-dimensional multitarget activity landscape. ( 0,92113655528467 )
J Chem Inf Model - Identification of novel malarial cysteine protease inhibitors using structure-based virtual screening of a focused cysteine protease inhibitor library. ( 0,919114329701888 )
J Chem Inf Model - Identification of novel liver X receptor activators by structure-based modeling. ( 0,917954216003294 )
J Chem Inf Model - Mining the ChEMBL database: an efficient chemoinformatics workflow for assembling an ion channel-focused screening library. ( 0,914989139131635 )
J Chem Inf Model - How diverse are diversity assessment methods? A comparative analysis and benchmarking of molecular descriptor space. ( 0,91356672482681 )
J Chem Inf Model - Introduction of target cliffs as a concept to identify and describe complex molecular selectivity patterns. ( 0,911981882740471 )
J Chem Inf Model - Identification of a novel inhibitor of dengue virus protease through use of a virtual screening drug discovery Web portal. ( 0,911443478745832 )
J Chem Inf Model - Ligand- and structure-based virtual screening for clathrodin-derived human voltage-gated sodium channel modulators. ( 0,910445248904779 )
J Chem Inf Model - Scaffold-focused virtual screening: prospective application to the discovery of TTK inhibitors. ( 0,909389182664853 )
J Chem Inf Model - A multivariate chemical similarity approach to search for drugs of potential environmental concern. ( 0,908945576417653 )
J Chem Inf Model - Capturing structure-activity relationships from chemogenomic spaces. ( 0,908836884097221 )
J Chem Inf Model - Visual characterization and diversity quantification of chemical libraries: 1. creation of delimited reference chemical subspaces. ( 0,908069582798138 )
J Chem Inf Model - Discovery of novel histamine H4 and serotonin transporter ligands using the topological feature tree descriptor. ( 0,907695129217702 )
J Chem Inf Model - Scaffold diversity of exemplified medicinal chemistry space. ( 0,907248338656417 )
J Chem Inf Model - Conditional probabilistic analysis for prediction of the activity landscape and relative compound activities. ( 0,907179133138149 )
J Chem Inf Model - Enumeration of 166 billion organic small molecules in the chemical universe database GDB-17. ( 0,907006987851106 )
J Chem Inf Model - De novo design of drug-like molecules by a fragment-based molecular evolutionary approach. ( 0,905962811089761 )
J Chem Inf Model - Discovery of a7-nicotinic receptor ligands by virtual screening of the chemical universe database GDB-13. ( 0,905534816768592 )
J Chem Inf Model - Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects. ( 0,905049118154338 )
J Chem Inf Model - Novel mycosin protease MycP1 inhibitors identified by virtual screening and 4D fingerprints. ( 0,903115840442484 )
J Chem Inf Model - Atom pair 2D-fingerprints perceive 3D-molecular shape and pharmacophores for very fast virtual screening of ZINC and GDB-17. ( 0,902151687721181 )
J Chem Inf Model - Identification of a new class of FtsZ inhibitors by structure-based design and in vitro screening. ( 0,899363075019541 )
J Chem Inf Model - Navigating high-dimensional activity landscapes: design and application of the ligand-target differentiation map. ( 0,897460747389198 )
J Chem Inf Model - Searching for recursively defined generic chemical patterns in nonenumerated fragment spaces. ( 0,892136937998786 )
J Chem Inf Model - Rationalizing the role of SAR tolerance for ligand-based virtual screening. ( 0,892056629473907 )
J Chem Inf Model - Selection of in silico drug screening results for G-protein-coupled receptors by using universal active probes. ( 0,891151380436799 )
J Chem Inf Model - Novel method for pharmacophore analysis by examining the joint pharmacophore space. ( 0,890266020457081 )
J Chem Inf Model - Fighting high molecular weight in bioactive molecules with sub-pharmacophore-based virtual screening. ( 0,889618167439279 )
J Chem Inf Model - Identification of novel serotonin transporter compounds by virtual screening. ( 0,889448734136566 )
J Chem Inf Model - Discovery and design of tricyclic scaffolds as protein kinase CK2 (CK2) inhibitors through a combination of shape-based virtual screening and structure-based molecular modification. ( 0,8890477082459 )
J Chem Inf Model - Multitarget structure-activity relationships characterized by activity-difference maps and consensus similarity measure. ( 0,88545778183485 )
J Chem Inf Model - Similarity boosted quantitative structure-activity relationship--a systematic study of enhancing structural descriptors by molecular similarity. ( 0,885283459091134 )
J Chem Inf Model - Molecular topology analysis of the differences between drugs, clinical candidate compounds, and bioactive molecules. ( 0,88339238098785 )
J Chem Inf Model - Extending the activity cliff concept: structural categorization of activity cliffs and systematic identification of different types of cliffs in the ChEMBL database. ( 0,883141626330765 )
J Chem Inf Model - Identification of sumoylation activating enzyme 1 inhibitors by structure-based virtual screening. ( 0,878506142552242 )
J Chem Inf Model - Fragment-based lead discovery and design. ( 0,878336016492193 )
J Chem Inf Model - Neighborhood-based prediction of novel active compounds from SAR matrices. ( 0,877982090303997 )
J Chem Inf Model - Scanning structure-activity relationships with structure-activity similarity and related maps: from consensus activity cliffs to selectivity switches. ( 0,875316510765131 )
J Chem Inf Model - Characterizing the diversity and biological relevance of the MLPCN assay manifold and screening set. ( 0,874195957701431 )
J Chem Inf Model - Discovery of new selective human aldose reductase inhibitors through virtual screening multiple binding pocket conformations. ( 0,873469378817014 )
J Chem Inf Model - BioSM: metabolomics tool for identifying endogenous mammalian biochemical structures in chemical structure space. ( 0,873337816644014 )
J Chem Inf Model - ColBioS-FlavRC: a collection of bioselective flavonoids and related compounds filtered from high-throughput screening outcomes. ( 0,872545061896464 )
J Chem Inf Model - Visualization and virtual screening of the chemical universe database GDB-17. ( 0,869190511774271 )
J Chem Inf Model - SMIfp (SMILES fingerprint) chemical space for virtual screening and visualization of large databases of organic molecules. ( 0,86904625759436 )
J Chem Inf Model - Identification of compounds with potential antibacterial activity against Mycobacterium through structure-based drug screening. ( 0,866771243344795 )
J Chem Inf Model - SABRE: ligand/structure-based virtual screening approach using consensus molecular-shape pattern recognition. ( 0,865808958115166 )
J Chem Inf Model - Structure based model for the prediction of phospholipidosis induction potential of small molecules. ( 0,865784033146203 )
J Chem Inf Model - Integrating medicinal chemistry, organic/combinatorial chemistry, and computational chemistry for the discovery of selective estrogen receptor modulators with Forecaster, a novel platform for drug discovery. ( 0,865051865972395 )
J Chem Inf Model - A searchable map of PubChem. ( 0,86481173381169 )
J Chem Inf Model - Structural similarity based kriging for quantitative structure activity and property relationship modeling. ( 0,859890639931513 )
Comput Biol Chem - The optimization of running time for a maximum common substructure-based algorithm and its application in drug design. ( 0,859173574427735 )
J Chem Inf Model - Prediction of new bioactive molecules using a Bayesian belief network. ( 0,858822847352301 )
J Chem Inf Model - Harvesting classification trees for drug discovery. ( 0,858454161498073 )
J Chem Inf Model - Knowledge-based libraries for predicting the geometric preferences of druglike molecules. ( 0,858267876256575 )
J Chem Inf Model - Enrichment of chemical libraries docked to protein conformational ensembles and application to aldehyde dehydrogenase 2. ( 0,856456234836344 )
J Chem Inf Model - Automatic tailoring and transplanting: a practical method that makes virtual screening more useful. ( 0,856187934293893 )
J Chem Inf Model - Identification of novel potential antibiotics against Staphylococcus using structure-based drug screening targeting dihydrofolate reductase. ( 0,855331694536743 )
J Chem Inf Model - Discovery of chemical compound groups with common structures by a network analysis approach (affinity prediction method). ( 0,854548333928431 )
J Chem Inf Model - A new protocol for predicting novel GSK-3? ATP competitive inhibitors. ( 0,853729304507892 )
J Am Med Inform Assoc - Drug repurposing: mining protozoan proteomes for targets of known bioactive compounds. ( 0,853445471332176 )
J Chem Inf Model - Similarity searching for potent compounds using feature selection. ( 0,851749979062973 )
J Chem Inf Model - Virtual screening yields inhibitors of novel antifungal drug target, benzoate 4-monooxygenase. ( 0,851298496620923 )
J Chem Inf Model - Freely available conformer generation methods: how good are they? ( 0,85023862450573 )
J Chem Inf Model - Systematic assessment of compound series with SAR transfer potential. ( 0,849918966954468 )
J Chem Inf Model - Feasibility of using molecular docking-based virtual screening for searching dual target kinase inhibitors. ( 0,849738446483122 )
J Chem Inf Model - Chemical data visualization and analysis with incremental generative topographic mapping: big data challenge. ( 0,848660067705579 )
J Chem Inf Model - Application of support vector machine to three-dimensional shape-based virtual screening using comprehensive three-dimensional molecular shape overlay with known inhibitors. ( 0,848267433462874 )
J Chem Inf Model - Rapid scanning structure-activity relationships in combinatorial data sets: identification of activity switches. ( 0,846472971489499 )
J Chem Inf Model - Prediction of activity cliffs using support vector machines. ( 0,846292773081833 )
J Chem Inf Model - Optimization of molecular representativeness. ( 0,846153021659522 )
J Chem Inf Model - Large-scale assessment of activity landscape feature probabilities of bioactive compounds. ( 0,846038858483052 )
J Chem Inf Model - Virtual fragment screening: discovery of histamine H3 receptor ligands using ligand-based and protein-based molecular fingerprints. ( 0,842321019521473 )
J Chem Inf Model - SAR monitoring of evolving compound data sets using activity landscapes. ( 0,838730894240242 )
J Chem Inf Model - How do 2D fingerprints detect structurally diverse active compounds? Revealing compound subset-specific fingerprint features through systematic selection. ( 0,836075434006335 )
J Chem Inf Model - Hsp90 inhibitors, part 2: combining ligand-based and structure-based approaches for virtual screening application. ( 0,833970945858326 )
J Chem Inf Model - Application of quantitative structure-activity relationship models of 5-HT1A receptor binding to virtual screening identifies novel and potent 5-HT1A ligands. ( 0,833277803669258 )
J Chem Inf Model - Bioturbo similarity searching: combining chemical and biological similarity to discover structurally diverse bioactive molecules. ( 0,83150227875559 )
J Chem Inf Model - Discovery of inhibitors of Schistosoma mansoni HDAC8 by combining homology modeling, virtual screening, and in vitro validation. ( 0,831402973376892 )
J Chem Inf Model - Shaping a screening file for maximal lead discovery efficiency and effectiveness: elimination of molecular redundancy. ( 0,831345544377319 )
J Integr Bioinform - Database supported candidate search for metabolite identification. ( 0,831007701300503 )
J Chem Inf Model - Construction and use of fragment-augmented molecular Hasse diagrams. ( 0,82962823194191 )