J Chem Inf Model - Fast protein binding site comparison via an index-based screening technology.

Tópicos

{ bind(1733) structur(1185) ligand(1036) }
{ compound(1573) activ(1297) structur(1058) }
{ method(1219) similar(1157) match(930) }
{ data(1737) use(1416) pattern(1282) }
{ care(1570) inform(1187) nurs(1089) }
{ featur(1941) imag(1645) propos(1176) }
{ model(2341) predict(2261) use(1141) }
{ can(774) often(719) complex(702) }
{ imag(1947) propos(1133) code(1026) }
{ imag(2675) segment(2577) method(1081) }
{ take(945) account(800) differ(722) }
{ assess(1506) score(1403) qualiti(1306) }
{ algorithm(1844) comput(1787) effici(935) }
{ model(3480) simul(1196) paramet(876) }
{ structur(1116) can(940) graph(676) }
{ high(1669) rate(1365) level(1280) }
{ featur(3375) classif(2383) classifi(1994) }
{ motion(1329) object(1292) video(1091) }
{ problem(2511) optim(1539) algorithm(950) }
{ method(1557) propos(1049) approach(1037) }
{ data(1714) softwar(1251) tool(1186) }
{ general(901) number(790) one(736) }
{ search(2224) databas(1162) retriev(909) }
{ studi(1410) differ(1259) use(1210) }
{ import(1318) role(1303) understand(862) }
{ visual(1396) interact(850) tool(830) }
{ perform(1367) use(1326) method(1137) }
{ studi(1119) effect(1106) posit(819) }
{ spatial(1525) area(1432) region(1030) }
{ ehr(2073) health(1662) electron(1139) }
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{ patient(2837) hospit(1953) medic(668) }
{ model(2656) set(1616) predict(1553) }
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{ age(1611) year(1155) adult(843) }
{ medic(1828) order(1363) alert(1069) }
{ signal(2180) analysi(812) frequenc(800) }
{ group(2977) signific(1463) compar(1072) }
{ gene(2352) biolog(1181) express(1162) }
{ data(3008) multipl(1320) sourc(1022) }
{ first(2504) two(1366) second(1323) }
{ intervent(3218) particip(2042) group(1664) }
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{ patient(1821) servic(1111) care(1106) }
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{ health(1844) social(1437) communiti(874) }
{ cancer(2502) breast(956) screen(824) }
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{ process(1125) use(805) approach(778) }
{ method(1969) cluster(1462) data(1082) }
{ method(2212) result(1239) propos(1039) }

Resumo

We present TrixP, a new index-based method for fast protein binding site comparison and function prediction. TrixP determines binding site similarities based on the comparison of descriptors that encode pharmacophoric and spatial features. Therefore, it adopts the efficient core components of TrixX, a structure-based virtual screening technology for large compound libraries. TrixP expands this technology by new components in order to allow a screening of protein libraries. TrixP accounts for the inherent flexibility of proteins employing a partial shape matching routine. After the identification of structures with matching pharmacophoric features and geometric shape, TrixP superimposes the binding sites and, finally, assesses their similarity according to the fit of pharmacophoric properties. TrixP is able to find analogies between closely and distantly related binding sites. Recovery rates of 81.8% for similar binding site pairs, assisted by rejecting rates of 99.5% for dissimilar pairs on a test data set containing 1331 pairs, confirm this ability. TrixP exclusively identifies members of the same protein family on top ranking positions out of a library consisting of 9802 binding sites. Furthermore, 30 predicted kinase binding sites can almost perfectly be classified into their known subfamilies.

Resumo Limpo

present trixp new indexbas method fast protein bind site comparison function predict trixp determin bind site similar base comparison descriptor encod pharmacophor spatial featur therefor adopt effici core compon trixx structurebas virtual screen technolog larg compound librari trixp expand technolog new compon order allow screen protein librari trixp account inher flexibl protein employ partial shape match routin identif structur match pharmacophor featur geometr shape trixp superimpos bind site final assess similar accord fit pharmacophor properti trixp abl find analog close distant relat bind site recoveri rate similar bind site pair assist reject rate dissimilar pair test data set contain pair confirm abil trixp exclus identifi member protein famili top rank posit librari consist bind site furthermor predict kinas bind site can almost perfect classifi known subfamili

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