J Chem Inf Model - Impact of template choice on homology model efficiency in virtual screening.

Tópicos

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

Resumo

Homology modeling is a reliable method of predicting the three-dimensional structures of proteins that lack NMR or X-ray crystallographic data. It employs the assumption that a structural resemblance exists between closely related proteins. Despite the availability of many crystal structures of possible templates, only the closest ones are chosen for homology modeling purposes. To validate the aforementioned approach, we performed homology modeling of four serotonin receptors (5-HT1AR, 5-HT2AR, 5-HT6R, 5-HT7R) for virtual screening purposes, using 10 available G-Protein Coupled Receptors (GPCR) templates with diverse evolutionary distances to the targets, with various approaches to alignment construction and model building. The resulting models were further validated in two steps by means of ligand docking and enrichment calculation, using Glide software. The final quality of the models was determined in virtual screening-like experiments by the AUROC score of the resulting ROC curves. The outcome of this research showed that no correlation between sequence identity and model quality was found, leading to the conclusion that the closest phylogenetic relative is not always the best template for homology modeling.

Resumo Limpo

homolog model reliabl method predict threedimension structur protein lack nmr xray crystallograph data employ assumpt structur resembl exist close relat protein despit avail mani crystal structur possibl templat closest one chosen homolog model purpos valid aforement approach perform homolog model four serotonin receptor htar htar htr htr virtual screen purpos use avail gprotein coupl receptor gpcr templat divers evolutionari distanc target various approach align construct model build result model valid two step mean ligand dock enrich calcul use glide softwar final qualiti model determin virtual screeninglik experi auroc score result roc curv outcom research show correl sequenc ident model qualiti found lead conclus closest phylogenet relat alway best templat homolog model

Resumos Similares

J Chem Inf Model - Robust scoring functions for protein-ligand interactions with quantum chemical charge models. ( 0,801318049446467 )
J Chem Inf Model - GRID-based three-dimensional pharmacophores II: PharmBench, a benchmark data set for evaluating pharmacophore elucidation methods. ( 0,791470066863432 )
J Chem Inf Model - CSAR data set release 2012: ligands, affinities, complexes, and docking decoys. ( 0,780097668050377 )
J Chem Inf Model - Development of novel 3D-QSAR combination approach for screening and optimizing B-Raf inhibitors in silico. ( 0,765877849630939 )
J Chem Inf Model - DrugPred: a structure-based approach to predict protein druggability developed using an extensive nonredundant data set. ( 0,762729393580196 )
J Chem Inf Model - Leave-cluster-out cross-validation is appropriate for scoring functions derived from diverse protein data sets. ( 0,754790869099078 )
J Chem Inf Model - Building a three-dimensional model of CYP2C9 inhibition using the Autocorrelator: an autonomous model generator. ( 0,754352035830533 )
J Chem Inf Model - Four-dimensional structure-activity relationship model to predict HIV-1 integrase strand transfer inhibition using LQTA-QSAR methodology. ( 0,752057045161327 )
J Chem Inf Model - Kinase-kernel models: accurate in silico screening of 4 million compounds across the entire human kinome. ( 0,747009638410671 )
J Chem Inf Model - iLOGP: a simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach. ( 0,727631636937518 )
J Chem Inf Model - Pharmacophore assessment through 3-D QSAR: evaluation of the predictive ability on new derivatives by the application on a series of antitubercular agents. ( 0,723579019822302 )
J Chem Inf Model - Time-split cross-validation as a method for estimating the goodness of prospective prediction. ( 0,712534131345129 )
Artif Intell Med - Training artificial neural networks directly on the concordance index for censored data using genetic algorithms. ( 0,701234805354735 )
J Chem Inf Model - Pharmacophore and 3D-QSAR characterization of 6-arylquinazolin-4-amines as Cdc2-like kinase 4 (Clk4) and dual specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A) inhibitors. ( 0,697339231979866 )
J Biomed Inform - MysiRNA: improving siRNA efficacy prediction using a machine-learning model combining multi-tools and whole stacking energy (G). ( 0,696810566832323 )
J Chem Inf Model - Study of chromatographic retention of natural terpenoids by chemoinformatic tools. ( 0,694023959299905 )
J Chem Inf Model - Does rational selection of training and test sets improve the outcome of QSAR modeling? ( 0,693432366831634 )
J Chem Inf Model - RS-Predictor models augmented with SMARTCyp reactivities: robust metabolic regioselectivity predictions for nine CYP isozymes. ( 0,692338699904934 )
J Chem Inf Model - Ligand-steered modeling and docking: A benchmarking study in class A G-protein-coupled receptors. ( 0,691653473838296 )
J Chem Inf Model - Combined 3D-QSAR, molecular docking, and molecular dynamics study on piperazinyl-glutamate-pyridines/pyrimidines as potent P2Y12 antagonists for inhibition of platelet aggregation. ( 0,690817363085634 )
J Chem Inf Model - Predicting ligand binding modes from neural networks trained on protein-ligand interaction fingerprints. ( 0,685042536234438 )
J Chem Inf Model - Subangstrom accuracy in pHLA-I modeling by Rosetta FlexPepDock refinement protocol. ( 0,684898695280363 )
J Chem Inf Model - PHOENIX: a scoring function for affinity prediction derived using high-resolution crystal structures and calorimetry measurements. ( 0,678412906011454 )
J Chem Inf Model - Assessing the performance of the MM/PBSA and MM/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations. ( 0,677806962467905 )
Comput Biol Chem - Homology modeling, binding site identification and docking in flavone hydroxylase CYP105P2 in Streptomyces peucetius ATCC 27952. ( 0,674309152217664 )
J Chem Inf Model - Predicting pK(a) values of substituted phenols from atomic charges: comparison of different quantum mechanical methods and charge distribution schemes. ( 0,670853168170877 )
J Chem Inf Model - Modeling, molecular dynamics simulation, and mutation validation for structure of cannabinoid receptor 2 based on known crystal structures of GPCRs. ( 0,670457327168168 )
J Chem Inf Model - Beyond the scope of Free-Wilson analysis: building interpretable QSAR models with machine learning algorithms. ( 0,668087372774139 )
J Chem Inf Model - Hsp90 inhibitors, part 1: definition of 3-D QSAutogrid/R models as a tool for virtual screening. ( 0,666652109880221 )
AMIA Annu Symp Proc - Effect of data combination on predictive modeling: a study using gene expression data. ( 0,66481664822317 )
Methods Inf Med - Quantifying changes in EEG complexity induced by photic stimulation. ( 0,659308546457413 )
J Chem Inf Model - Prediction of ligand-induced structural polymorphism of receptor interaction sites using machine learning. ( 0,656911338348901 )
J Chem Inf Model - Rank order entropy: why one metric is not enough. ( 0,656416034228358 )
BMC Med Inform Decis Mak - Regression tree construction by bootstrap: model search for DRG-systems applied to Austrian health-data. ( 0,650688761406862 )
J Chem Inf Model - A multiscale simulation system for the prediction of drug-induced cardiotoxicity. ( 0,646579046120533 )
BMC Med Inform Decis Mak - Concordance and predictive value of two adverse drug event data sets. ( 0,644409662638105 )
J Chem Inf Model - Three-dimensional pharmacophore modeling of liver-X receptor agonists. ( 0,644208460196306 )
Comput Methods Programs Biomed - Sequence-based prediction of protein-binding sites in DNA: comparative study of two SVM models. ( 0,642295184639047 )
J Chem Inf Model - New strategy for receptor-based pharmacophore query construction: a case study for 5-HT7 receptor ligands. ( 0,641303220953516 )
J Chem Inf Model - In silico prediction of aqueous solubility using simple QSPR models: the importance of phenol and phenol-like moieties. ( 0,640796029314865 )
J Chem Inf Model - Uniting cheminformatics and chemical theory to predict the intrinsic aqueous solubility of crystalline druglike molecules. ( 0,63861282317291 )
J Chem Inf Model - Extensive consensus docking evaluation for ligand pose prediction and virtual screening studies. ( 0,636579056352535 )
J Chem Inf Model - Introducing conformal prediction in predictive modeling. A transparent and flexible alternative to applicability domain determination. ( 0,636538529609189 )
J Chem Inf Model - Docking-based comparative intermolecular contacts analysis as new 3-D QSAR concept for validating docking studies and in silico screening: NMT and GP inhibitors as case studies. ( 0,63353596036397 )
Neural Comput - Molecular diffusion model of neurotransmitter homeostasis around synapses supporting gradients. ( 0,629450123121259 )
J Chem Inf Model - Combined application of cheminformatics- and physical force field-based scoring functions improves binding affinity prediction for CSAR data sets. ( 0,62864759944493 )
J Chem Inf Model - In silico prediction of total human plasma clearance. ( 0,626823748012146 )
J Chem Inf Model - Potency prediction of ?-secretase (BACE-1) inhibitors using density functional methods. ( 0,626507607990633 )
J Chem Inf Model - A machine learning-based method to improve docking scoring functions and its application to drug repurposing. ( 0,625741713814243 )
AMIA Annu Symp Proc - Motivating the additional use of external validity: examining transportability in a model of glioblastoma multiforme. ( 0,622267529832993 )
Comput Biol Chem - A new protein graph model for function prediction. ( 0,621033611734989 )
J. Comput. Biol. - The complexity of the dirichlet model for multiple alignment data. ( 0,620652019303558 )
AMIA Annu Symp Proc - Predicting the dengue incidence in Singapore using univariate time series models. ( 0,620206069554407 )
Comput Biol Chem - Targeting the Akt1 allosteric site to identify novel scaffolds through virtual screening. ( 0,619644288579021 )
J Chem Inf Model - Comparative studies on some metrics for external validation of QSPR models. ( 0,618337584151995 )
J Chem Inf Model - Understanding the impact of the P-loop conformation on kinase selectivity. ( 0,616128094511126 )
J. Med. Internet Res. - A case study of the New York City 2012-2013 influenza season with daily geocoded Twitter data from temporal and spatiotemporal perspectives. ( 0,61597665122797 )
J Chem Inf Model - Revisiting a receptor-based pharmacophore hypothesis for human A(2A) adenosine receptor antagonists. ( 0,61421664279992 )
J Chem Inf Model - Best of both worlds: combining pharma data and state of the art modeling technology to improve in Silico pKa prediction. ( 0,611021202922961 )
J Chem Inf Model - Acetylcholinesterase inhibitors: structure based design, synthesis, pharmacophore modeling, and virtual screening. ( 0,610936266809534 )
J Chem Inf Model - Improving the scoring of protein-ligand binding affinity by including the effects of structural water and electronic polarization. ( 0,609968610771922 )
Brief. Bioinformatics - A reversed framework for the identification of microRNA-target pairs in plants. ( 0,609534157538521 )
J Chem Inf Model - In silico prediction of chemical Ames mutagenicity. ( 0,60945306175084 )
Artif Intell Med - Fuzzy model identification of dengue epidemic in Colombia based on multiresolution analysis. ( 0,608525262336255 )
J Chem Inf Model - Structure-based prediction of subtype selectivity of histamine H3 receptor selective antagonists in clinical trials. ( 0,608099161404871 )
J Am Med Inform Assoc - Harvest: an open platform for developing web-based biomedical data discovery and reporting applications. ( 0,607499412375798 )
J Chem Inf Model - Analyzing the topology of active sites: on the prediction of pockets and subpockets. ( 0,605978584860328 )
J Chem Inf Model - Combined receptor and ligand-based approach to the universal pharmacophore model development for studies of drug blockade to the hERG1 pore domain. ( 0,60541254297921 )
Curr Comput Aided Drug Des - QSAR Models for the Reactivation of Sarin Inhibited AChE by Quaternary Pyridinium Oximes Based on Monte Carlo Method. ( 0,603971363098884 )
J Chem Inf Model - Global free energy scoring functions based on distance-dependent atom-type pair descriptors. ( 0,603893952688188 )
BMC Med Inform Decis Mak - Measuring preferences for analgesic treatment for cancer pain: how do African-Americans and Whites perform on choice-based conjoint (CBC) analysis experiments? ( 0,603791693668834 )
J Chem Inf Model - Functional prediction of binding pockets. ( 0,603373877728536 )
J Chem Inf Model - Quantitatively interpreted enhanced inhibition of cytochrome P450s by heteroaromatic rings containing nitrogen. ( 0,601725672666089 )
Comput. Biol. Med. - A prediction model of substrates and non-substrates of breast cancer resistance protein (BCRP) developed by GA-CG-SVM method. ( 0,601683188623057 )
J Chem Inf Model - Modeling of open, closed, and open-inactivated states of the hERG1 channel: structural mechanisms of the state-dependent drug binding. ( 0,599675263824336 )
J Chem Inf Model - Three useful dimensions for domain applicability in QSAR models using random forest. ( 0,599649960536752 )
AMIA Annu Symp Proc - Advanced proficiency EHR training: effect on physicians' EHR efficiency, EHR satisfaction and job satisfaction. ( 0,599288891243429 )
J Chem Inf Model - Experimental and computational prediction of glass transition temperature of drugs. ( 0,598033473081374 )
Comput. Biol. Med. - Artificial neural network modelling of the results of tympanoplasty in chronic suppurative otitis media patients. ( 0,595940016478802 )
Comput. Aided Surg. - Evaluation of a computational model to predict elbow range of motion. ( 0,595603487292755 )
J Chem Inf Model - Docking studies on DNA intercalators. ( 0,594071667145601 )
J Chem Inf Model - Rationalization of the pKa values of alcohols and thiols using atomic charge descriptors and its application to the prediction of amino acid pKa's. ( 0,593653767459367 )
Int J Health Geogr - Comparative analysis of remotely-sensed data products via ecological niche modeling of avian influenza case occurrences in Middle Eastern poultry. ( 0,593447944671615 )
J Chem Inf Model - MARS: computing three-dimensional alignments for multiple ligands using pairwise similarities. ( 0,593350599249928 )
Comput Methods Programs Biomed - Kinetic modelling of haemodialysis removal of myoglobin in rhabdomyolysis patients. ( 0,592148313194352 )
J Chem Inf Model - New aryl hydrocarbon receptor homology model targeted to improve docking reliability. ( 0,591891385727592 )
J Chem Inf Model - The assembly-inducing laulimalide/peloruside a binding site on tubulin: molecular modeling and biochemical studies with [?H]peloruside A. ( 0,591552805607786 )
J Chem Inf Model - Comparison of random forest and Pipeline Pilot Na?ve Bayes in prospective QSAR predictions. ( 0,590882052138332 )
J Chem Inf Model - Criterion for evaluating the predictive ability of nonlinear regression models without cross-validation. ( 0,590298307830024 )
J Chem Inf Model - Kernel-based partial least squares: application to fingerprint-based QSAR with model visualization. ( 0,589654021982161 )
J Chem Inf Model - Computational screening for active compounds targeting protein sequences: methodology and experimental validation. ( 0,586854291590467 )
J Integr Bioinform - Predicting protein distance maps according to physicochemical properties. ( 0,584918940873658 )
J Chem Inf Model - Classification of compounds with distinct or overlapping multi-target activities and diverse molecular mechanisms using emerging chemical patterns. ( 0,584443030214947 )
Artif Intell Med - PMirP: a pre-microRNA prediction method based on structure-sequence hybrid features. ( 0,584209505200544 )
J Integr Bioinform - An integrative approach to modeling biological networks. ( 0,582736534281402 )
J Chem Inf Model - Design and synthesis of new antioxidants predicted by the model developed on a set of pulvinic acid derivatives. ( 0,58065401110517 )
Int J Health Geogr - Incorporating geographical factors with artificial neural networks to predict reference values of erythrocyte sedimentation rate. ( 0,579731781582629 )
J Chem Inf Model - MM/GBSA binding energy prediction on the PDBbind data set: successes, failures, and directions for further improvement. ( 0,57917581807048 )
J Chem Inf Model - Statistical analysis and compound selection of combinatorial libraries for soluble epoxide hydrolase. ( 0,578242717268052 )
J Chem Inf Model - Template CoMFA applied to 116 biological targets. ( 0,578034521580731 )