J Chem Inf Model - Searching for recursively defined generic chemical patterns in nonenumerated fragment spaces.

Tópicos

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

Retrieving molecules with specific structural features is a fundamental requirement of today's molecular database technologies. Estimates claim the chemical space relevant for drug discovery to be around 106? molecules. This figure is many orders of magnitude larger than the amount of molecules conventional databases retain today and will store in the future. An elegant description of such a large chemical space is provided by the concept of fragment spaces. A fragment space comprises fragments that are molecules with open valences and describes rules how to connect these fragments to products. Due to the combinatorial nature of fragment spaces, a complete enumeration of its products is intractable. We present an algorithm to search fragment spaces for generic chemical patterns as present in the SMARTS chemical pattern language. Our method allows specification of the chemical surrounding of an atom in a query and, therefore, enables a chemically intuitive search. During the search, the costly enumeration of products is avoided. The result is a fragment space that exactly describes all possible molecules that contain the user-defined pattern. We evaluated the algorithm in three different drug development use-cases and performed a large scale statistical analysis with 738 SMARTS patterns on three public available fragment spaces. Our results show the ability of the algorithm to explore the chemical space around known active molecules, to analyze fragment spaces for the presence of likely toxic molecules, and to identify complex macromolecular structures under additional structural constraints. By searching the fragment space in its nonenumerated form, spaces covering up to 10? molecules can be examined in times ranging between 47 s and 19 min depending on the complexity of the query pattern.

Resumo Limpo

retriev molecul specif structur featur fundament requir today molecular databas technolog estim claim chemic space relev drug discoveri around molecul figur mani order magnitud larger amount molecul convent databas retain today will store futur eleg descript larg chemic space provid concept fragment space fragment space compris fragment molecul open valenc describ rule connect fragment product due combinatori natur fragment space complet enumer product intract present algorithm search fragment space generic chemic pattern present smart chemic pattern languag method allow specif chemic surround atom queri therefor enabl chemic intuit search search cost enumer product avoid result fragment space exact describ possibl molecul contain userdefin pattern evalu algorithm three differ drug develop usecas perform larg scale statist analysi smart pattern three public avail fragment space result show abil algorithm explor chemic space around known activ molecul analyz fragment space presenc like toxic molecul identifi complex macromolecular structur addit structur constraint search fragment space nonenumer form space cover molecul can examin time rang s min depend complex queri pattern

Resumos Similares

J Chem Inf Model - Ligand- and structure-based virtual screening for clathrodin-derived human voltage-gated sodium channel modulators. ( 0,944847718430522 )
J Chem Inf Model - Identifying compound-target associations by combining bioactivity profile similarity search and public databases mining. ( 0,942381039949581 )
J Chem Inf Model - In silico enzymatic synthesis of a 400,000 compound biochemical database for nontargeted metabolomics. ( 0,92402248116614 )
J Chem Inf Model - Target-independent prediction of drug synergies using only drug lipophilicity. ( 0,916685300384924 )
J Chem Inf Model - Discovery of a7-nicotinic receptor ligands by virtual screening of the chemical universe database GDB-13. ( 0,911915490445184 )
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. ( 0,911205818569095 )
J Chem Inf Model - Identification of novel malarial cysteine protease inhibitors using structure-based virtual screening of a focused cysteine protease inhibitor library. ( 0,911088326335898 )
J Chem Inf Model - Increasing the coverage of medicinal chemistry-relevant space in commercial fragments screening. ( 0,911077783964466 )
J Chem Inf Model - Polypharmacology directed compound data mining: identification of promiscuous chemotypes with different activity profiles and comparison to approved drugs. ( 0,910175476444588 )
J Chem Inf Model - Automated recycling of chemistry for virtual screening and library design. ( 0,908609213692284 )
J Chem Inf Model - G-protein coupled receptors virtual screening using genetic algorithm focused chemical space. ( 0,908274814066157 )
J Chem Inf Model - Identification of 1,2,5-oxadiazoles as a new class of SENP2 inhibitors using structure based virtual screening. ( 0,905303934696009 )
J Chem Inf Model - TIN-a combinatorial compound collection of synthetically feasible multicomponent synthesis products. ( 0,903962659154674 )
J Chem Inf Model - Fighting high molecular weight in bioactive molecules with sub-pharmacophore-based virtual screening. ( 0,902049760462284 )
J Chem Inf Model - Compound optimization through data set-dependent chemical transformations. ( 0,90196436859633 )
J Chem Inf Model - Identification of a novel inhibitor of dengue virus protease through use of a virtual screening drug discovery Web portal. ( 0,897825841800334 )
J Chem Inf Model - Identification of multitarget activity ridges in high-dimensional bioactivity spaces. ( 0,897029325130454 )
J Chem Inf Model - Identification of novel liver X receptor activators by structure-based modeling. ( 0,896836154058315 )
J Chem Inf Model - Natural product-like virtual libraries: recursive atom-based enumeration. ( 0,894989466916317 )
J Chem Inf Model - Mining the ChEMBL database: an efficient chemoinformatics workflow for assembling an ion channel-focused screening library. ( 0,893293709533413 )
J Chem Inf Model - Conditional probabilistic analysis for prediction of the activity landscape and relative compound activities. ( 0,893110008834326 )
Curr Comput Aided Drug Des - Development of Chemical Compound Libraries for In Silico Drug Screening. ( 0,892843017540572 )
J Chem Inf Model - Visualization and virtual screening of the chemical universe database GDB-17. ( 0,892731296590356 )
J Chem Inf Model - Discovery of novel histamine H4 and serotonin transporter ligands using the topological feature tree descriptor. ( 0,892362752720914 )
J Chem Inf Model - Combining horizontal and vertical substructure relationships in scaffold hierarchies for activity prediction. ( 0,892136937998786 )
J Chem Inf Model - Enumeration of 166 billion organic small molecules in the chemical universe database GDB-17. ( 0,891255052228739 )
J Chem Inf Model - Scaffold-focused virtual screening: prospective application to the discovery of TTK inhibitors. ( 0,889197706505014 )
J Chem Inf Model - Introduction of target cliffs as a concept to identify and describe complex molecular selectivity patterns. ( 0,888400033207501 )
J Chem Inf Model - How do 2D fingerprints detect structurally diverse active compounds? Revealing compound subset-specific fingerprint features through systematic selection. ( 0,888146246141275 )
J Chem Inf Model - From activity cliffs to activity ridges: informative data structures for SAR analysis. ( 0,887894370102943 )
J Chem Inf Model - Visual characterization and diversity quantification of chemical libraries: 1. creation of delimited reference chemical subspaces. ( 0,887270276805483 )
J Chem Inf Model - Identification of sumoylation activating enzyme 1 inhibitors by structure-based virtual screening. ( 0,887104444378325 )
J Chem Inf Model - Novel mycosin protease MycP1 inhibitors identified by virtual screening and 4D fingerprints. ( 0,886324872859022 )
J Chem Inf Model - Navigating high-dimensional activity landscapes: design and application of the ligand-target differentiation map. ( 0,886155256803174 )
J Chem Inf Model - Design of a three-dimensional multitarget activity landscape. ( 0,885834773677587 )
J Chem Inf Model - Novel method for pharmacophore analysis by examining the joint pharmacophore space. ( 0,885834246677692 )
J Chem Inf Model - Compound set enrichment: a novel approach to analysis of primary HTS data. ( 0,884254525388538 )
J Chem Inf Model - Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects. ( 0,884233607399286 )
J Chem Inf Model - Capturing structure-activity relationships from chemogenomic spaces. ( 0,884225706343519 )
J Chem Inf Model - How diverse are diversity assessment methods? A comparative analysis and benchmarking of molecular descriptor space. ( 0,884087465691336 )
J Chem Inf Model - Searching for substructures in fragment spaces. ( 0,884011728873698 )
J Chem Inf Model - Scaffold diversity of exemplified medicinal chemistry space. ( 0,882693975222849 )
J Chem Inf Model - Scanning structure-activity relationships with structure-activity similarity and related maps: from consensus activity cliffs to selectivity switches. ( 0,87742745904148 )
J Chem Inf Model - Similarity searching for potent compounds using feature selection. ( 0,874512207013352 )
J Chem Inf Model - Design of multitarget activity landscapes that capture hierarchical activity cliff distributions. ( 0,873742166537675 )
J Chem Inf Model - Similarity boosted quantitative structure-activity relationship--a systematic study of enhancing structural descriptors by molecular similarity. ( 0,872853755807278 )
J Chem Inf Model - QSAR classification model for antibacterial compounds and its use in virtual screening. ( 0,872105432458263 )
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. ( 0,871855203381052 )
J Chem Inf Model - De novo design of drug-like molecules by a fragment-based molecular evolutionary approach. ( 0,871803630219538 )
J Chem Inf Model - Prediction of individual compounds forming activity cliffs using emerging chemical patterns. ( 0,871476168469526 )
J Chem Inf Model - Characterizing the diversity and biological relevance of the MLPCN assay manifold and screening set. ( 0,871351414846705 )
J Chem Inf Model - Feasibility of using molecular docking-based virtual screening for searching dual target kinase inhibitors. ( 0,868872748986506 )
J Chem Inf Model - Identification of novel serotonin transporter compounds by virtual screening. ( 0,86819260989274 )
J Chem Inf Model - Identification of descriptors capturing compound class-specific features by mutual information analysis. ( 0,867739415641796 )
J Chem Inf Model - Identification of a new class of FtsZ inhibitors by structure-based design and in vitro screening. ( 0,864998492626938 )
J Chem Inf Model - Atom pair 2D-fingerprints perceive 3D-molecular shape and pharmacophores for very fast virtual screening of ZINC and GDB-17. ( 0,864978290489167 )
J Chem Inf Model - Selection of in silico drug screening results for G-protein-coupled receptors by using universal active probes. ( 0,864408916772131 )
J Chem Inf Model - A multivariate chemical similarity approach to search for drugs of potential environmental concern. ( 0,86312996629675 )
J Chem Inf Model - Discovery of new selective human aldose reductase inhibitors through virtual screening multiple binding pocket conformations. ( 0,860280245224343 )
J Chem Inf Model - A searchable map of PubChem. ( 0,860118873365418 )
J Chem Inf Model - Rationalizing the role of SAR tolerance for ligand-based virtual screening. ( 0,858250277962227 )
Comput Biol Chem - The optimization of running time for a maximum common substructure-based algorithm and its application in drug design. ( 0,857547123467314 )
J Chem Inf Model - Neighborhood-based prediction of novel active compounds from SAR matrices. ( 0,857350186200802 )
J Integr Bioinform - Database supported candidate search for metabolite identification. ( 0,856073868044087 )
J Chem Inf Model - SABRE: ligand/structure-based virtual screening approach using consensus molecular-shape pattern recognition. ( 0,85558088630883 )
J Chem Inf Model - Multitarget structure-activity relationships characterized by activity-difference maps and consensus similarity measure. ( 0,85552405107228 )
J Chem Inf Model - Identification of novel potential antibiotics against Staphylococcus using structure-based drug screening targeting dihydrofolate reductase. ( 0,854706464711593 )
J Chem Inf Model - A new protocol for predicting novel GSK-3? ATP competitive inhibitors. ( 0,851436501285463 )
J Chem Inf Model - Identification of compounds with potential antibacterial activity against Mycobacterium through structure-based drug screening. ( 0,848824956767895 )
J Chem Inf Model - Bioturbo similarity searching: combining chemical and biological similarity to discover structurally diverse bioactive molecules. ( 0,848783327620439 )
J Chem Inf Model - Enrichment of chemical libraries docked to protein conformational ensembles and application to aldehyde dehydrogenase 2. ( 0,848656413242325 )
J Chem Inf Model - Molecular topology analysis of the differences between drugs, clinical candidate compounds, and bioactive molecules. ( 0,848323689264026 )
J Chem Inf Model - Fragment-based lead discovery and design. ( 0,847669829186708 )
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. ( 0,847245534124966 )
J Chem Inf Model - Automatic tailoring and transplanting: a practical method that makes virtual screening more useful. ( 0,846795299717168 )
J Am Med Inform Assoc - Drug repurposing: mining protozoan proteomes for targets of known bioactive compounds. ( 0,846709493214206 )
J Chem Inf Model - ColBioS-FlavRC: a collection of bioselective flavonoids and related compounds filtered from high-throughput screening outcomes. ( 0,846211377176132 )
J Chem Inf Model - FINDSITE(comb): a threading/structure-based, proteomic-scale virtual ligand screening approach. ( 0,844564262650746 )
J Chem Inf Model - Structural similarity based kriging for quantitative structure activity and property relationship modeling. ( 0,843107549273698 )
J Chem Inf Model - Hit expansion approaches using multiple similarity methods and virtualized query structures. ( 0,842253817627593 )
J Chem Inf Model - BioSM: metabolomics tool for identifying endogenous mammalian biochemical structures in chemical structure space. ( 0,842169772306035 )
J Chem Inf Model - Virtual screening yields inhibitors of novel antifungal drug target, benzoate 4-monooxygenase. ( 0,839031030661794 )
J Chem Inf Model - Discovery of chemical compound groups with common structures by a network analysis approach (affinity prediction method). ( 0,836520008621473 )
J Chem Inf Model - SMIfp (SMILES fingerprint) chemical space for virtual screening and visualization of large databases of organic molecules. ( 0,835543024979832 )
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. ( 0,834981347869673 )
J Chem Inf Model - Multiple e-pharmacophore modeling, 3D-QSAR, and high-throughput virtual screening of hepatitis C virus NS5B polymerase inhibitors. ( 0,834335499438181 )
J Chem Inf Model - Construction and use of fragment-augmented molecular Hasse diagrams. ( 0,833760251827633 )
J Chem Inf Model - SAR monitoring of evolving compound data sets using activity landscapes. ( 0,832630034898144 )
J Chem Inf Model - Prediction of new bioactive molecules using a Bayesian belief network. ( 0,831689317910295 )
J Chem Inf Model - Systematic assessment of compound series with SAR transfer potential. ( 0,831029472525532 )
J Chem Inf Model - MQN-mapplet: visualization of chemical space with interactive maps of DrugBank, ChEMBL, PubChem, GDB-11, and GDB-13. ( 0,830765308184983 )
J Chem Inf Model - Discovery of inhibitors of Schistosoma mansoni HDAC8 by combining homology modeling, virtual screening, and in vitro validation. ( 0,830604473482353 )
J Chem Inf Model - Prediction of activity cliffs using support vector machines. ( 0,828966400057941 )
J Chem Inf Model - Molecular modeling of potential anticancer agents from African medicinal plants. ( 0,82879410364763 )
J Chem Inf Model - Prediction of synthetic accessibility based on commercially available compound databases. ( 0,826995567486279 )
J Chem Inf Model - Docking ligands into flexible and solvated macromolecules. 7. Impact of protein flexibility and water molecules on docking-based virtual screening accuracy. ( 0,826774652489645 )
J Chem Inf Model - Large-scale assessment of activity landscape feature probabilities of bioactive compounds. ( 0,825944372563231 )
J Chem Inf Model - Computational repositioning and experimental validation of approved drugs for HIF-prolyl hydroxylase inhibition. ( 0,825418609047632 )
J Chem Inf Model - Virtual fragment screening: discovery of histamine H3 receptor ligands using ligand-based and protein-based molecular fingerprints. ( 0,824910442381173 )
J Chem Inf Model - Do not hesitate to use Tversky-and other hints for successful active analogue searches with feature count descriptors. ( 0,823390105498934 )