J Chem Inf Model - DrugPred: a structure-based approach to predict protein druggability developed using an extensive nonredundant data set.

Tópicos

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

Resumo

Judging if a protein is able to bind orally available molecules with high affinity, i.e. if a protein is druggable, is an important step in target assessment. In order to derive a structure-based method to predict protein druggability, a comprehensive, nonredundant data set containing crystal structures of 71 druggable and 44 less druggable proteins was compiled by literature search and data mining. This data set was subsequently used to train a structure-based druggability predictor (DrugPred) using partial least-squares projection to latent structures discriminant analysis (PLS-DA). DrugPred performed well in discriminating druggable from less druggable binding sites for both internal and external predictions. The method is robust against conformational changes in the binding site and outperforms previously published methods. The superior performance of DrugPred is likely due to the size and composition of the training set which, in contrast to most previously developed methods, only contains cavities that have evolved to bind a natural ligand.

Resumo Limpo

judg protein abl bind oral avail molecul high affin ie protein druggabl import step target assess order deriv structurebas method predict protein druggabl comprehens nonredund data set contain crystal structur druggabl less druggabl protein compil literatur search data mine data set subsequ use train structurebas druggabl predictor drugpr use partial leastsquar project latent structur discrimin analysi plsda drugpr perform well discrimin druggabl less druggabl bind site intern extern predict method robust conform chang bind site outperform previous publish method superior perform drugpr like due size composit train set contrast previous develop method contain caviti evolv bind natur ligand

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