{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T12:47:56Z","timestamp":1781786876091,"version":"3.54.5"},"reference-count":63,"publisher":"American Chemical Society (ACS)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Chem. Inf. Model."],"published-print":{"date-parts":[[2010,6,28]]},"DOI":"10.1021\/ci100049h","type":"journal-article","created":{"date-parts":[[2010,6,4]],"date-time":"2010-06-04T20:06:52Z","timestamp":1275682012000},"page":"1101-1112","source":"Crossref","is-referenced-by-count":34,"title":["Computational Study on the Interaction of N1 Substituted Pyrazole Derivatives with B-Raf Kinase: An Unusual Water Wire Hydrogen-Bond Network and Novel Interactions at the Entrance of the Active Site"],"prefix":"10.1021","volume":"50","author":[{"given":"Jans H.","family":"Alzate-Morales","sequence":"first","affiliation":[{"name":"Centro de Bioinform\u00e1tica y Simulaci\u00f3n Molecular, Universidad de Talca, 2 Norte 685, Casilla 721, Talca, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariela","family":"Vergara-Jaque","sequence":"additional","affiliation":[{"name":"Centro de Bioinform\u00e1tica y Simulaci\u00f3n Molecular, Universidad de Talca, 2 Norte 685, Casilla 721, Talca, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Caballero","sequence":"additional","affiliation":[{"name":"Centro de Bioinform\u00e1tica y Simulaci\u00f3n Molecular, Universidad de Talca, 2 Norte 685, Casilla 721, Talca, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2010,6,4]]},"reference":[{"key":"ref1\/cit1","first-page":"25","volume":"1653","author":"Mercer K. E.","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"ref2\/cit2","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.ccr.2004.09.022","volume":"6","author":"Garnett M. J.","year":"2004","journal-title":"Cancer Cell"},{"key":"ref3\/cit3","first-page":"452","volume":"8","author":"Li N.","year":"2007","journal-title":"Curr. Opin. Invest. Drugs"},{"key":"ref4\/cit4","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.uct.2007.10.001","volume":"2","author":"Ramnath N.","year":"2007","journal-title":"Update Cancer Ther."},{"key":"ref5\/cit5","unstructured":"Safety Study of PLX4032 in Patients With Solid Tumors.Clinical Trials;National Institutes of Health:Bethesda, MD;ClinicalTrials.gov; Identifier: NCT00405587."},{"key":"ref6\/cit6","unstructured":"Study of XL281 in Adults With Solid Tumors.Clinical Trials;National Institutes of Health:Bethesda, MD;ClinicalTrials.gov; Identifier: NCT00451880."},{"key":"ref7\/cit7","unstructured":"A Phase I Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of GSK2118436 in Subjects With Solid Tumors.Clinical Trials;National Institutes of Health:Bethesda, MD;ClinicalTrials.gov; Identifier: NCT00880321."},{"key":"ref8\/cit8","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1021\/ci8004034","volume":"49","author":"Alzate-Morales J. H.","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"ref9\/cit9","doi-asserted-by":"crossref","first-page":"6543","DOI":"10.1021\/jm901330e","volume":"52","author":"Larsen C. A.","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref10\/cit10","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1021\/ci050263i","volume":"45","author":"Fernandez M.","year":"2005","journal-title":"J. Chem. Inf. Model."},{"key":"ref11\/cit11","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s11538-005-9006-3","volume":"68","author":"Gonz\u00e1lez M.","year":"2006","journal-title":"Bull. Math. Biol."},{"key":"ref12\/cit12","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.bmc.2007.10.024","volume":"16","author":"Caballero J.","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"ref13\/cit13","doi-asserted-by":"crossref","first-page":"6103","DOI":"10.1016\/j.bmc.2008.04.048","volume":"16","author":"Caballero J.","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"ref14\/cit14","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1016\/j.bmc.2007.11.053","volume":"16","author":"Gueto C.","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"ref15\/cit15","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1021\/ci900302z","volume":"50","author":"Alzate-Morales J.","year":"2010","journal-title":"J. Chem. Inf. Model"},{"key":"ref16\/cit16","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/j.jmgm.2007.11.005","volume":"26","author":"Muthas D.","year":"2008","journal-title":"J. Mol. Graph. Model."},{"key":"ref17\/cit17","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1016\/j.bmcl.2009.02.049","volume":"19","author":"Xie H. Z.","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref18\/cit18","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1039\/b719959g","volume":"6","author":"Uno M.","year":"2008","journal-title":"Org. Biomol. Chem."},{"key":"ref19\/cit19","doi-asserted-by":"crossref","first-page":"6456","DOI":"10.1021\/jm901147e","volume":"52","author":"Vieth M.","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref20\/cit20","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1529\/biophysj.106.091512","volume":"92","author":"Alzate-Morales J. H.","year":"2007","journal-title":"Biophys. J."},{"key":"ref21\/cit21","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1021\/ci900022h","volume":"49","author":"Gleeson M. P.","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"ref22\/cit22","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.cplett.2009.08.020","volume":"479","author":"Alzate-Morales J. H.","year":"2009","journal-title":"Chem. Phys. Lett."},{"key":"ref23\/cit23","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1080\/07391102.2002.10506853","volume":"20","author":"Villaca\u00f1as O.","year":"2002","journal-title":"J. Biomol. Struct. Dynamics"},{"key":"ref24\/cit24","doi-asserted-by":"crossref","first-page":"6121","DOI":"10.1021\/jm800539g","volume":"51","author":"Luo C.","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref25\/cit25","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1021\/mp8001107","volume":"6","author":"Fratev F.","year":"2009","journal-title":"Mol. Pharmaceutics"},{"key":"ref26\/cit26","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1472-6807-9-47","volume":"9","author":"Fratev F.","year":"2009","journal-title":"BMC Struct. Biol."},{"key":"ref27\/cit27","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1016\/j.bbamcr.2009.09.001","volume":"1793","author":"Moretti S.","year":"2009","journal-title":"Biochim. Biophys. Acta, Mol. Cell Res."},{"key":"ref28\/cit28","doi-asserted-by":"crossref","first-page":"4692","DOI":"10.1016\/j.bmcl.2008.07.002","volume":"18","author":"Hansen J. D.","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref29\/cit29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1023\/A:1016345810973","volume":"16","author":"Hou T.","year":"2002","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref30\/cit30","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.1021\/jm0309194","volume":"46","author":"Zaheer-ul-haq; Wellenzohn B.","year":"2003","journal-title":"J. Med. Chem."},{"key":"ref31\/cit31","doi-asserted-by":"crossref","first-page":"573","DOI":"10.3233\/JAD-2010-1262","volume":"19","author":"Rojo L. E.","year":"2010","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref32\/cit32","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1021\/jm011075w","volume":"45","author":"Pedretti A.","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref33\/cit33","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s11030-009-9140-1","volume":"13","author":"Caballero J.","year":"2009","journal-title":"Mol. Diversity"},{"key":"ref34\/cit34","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1002\/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B","volume":"19","author":"Morris G. M.","year":"1998","journal-title":"J. Comput. Chem."},{"key":"ref35\/cit35","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","volume":"47","author":"Friesner R. A.","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref36\/cit36","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/jcc.540150503","volume":"15","author":"Abagyan R.","year":"1994","journal-title":"J. Comput. Chem."},{"key":"ref37\/cit37","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1021\/jm020406h","volume":"46","author":"Jain A. N.","year":"2003","journal-title":"J. Med. Chem."},{"key":"ref38\/cit38","unstructured":"Epik, version 1.5;Schr\u00f6dinger, LLC:New York, NY, 2007."},{"key":"ref39\/cit39","doi-asserted-by":"crossref","first-page":"3902","DOI":"10.1021\/ja00299a024","volume":"107","author":"Dewar M. J. S.","year":"1985","journal-title":"J. Am. Chem. Soc."},{"key":"ref40\/cit40","unstructured":"Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A.Gaussian 03Gaussian, Inc.:Wallingford, CT, 2004."},{"key":"ref41\/cit41","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/S0076-6879(03)74020-8","volume":"374","author":"Fiser A.","year":"2003","journal-title":"Methods Enzymol."},{"key":"ref42\/cit42","unstructured":"Maestro, version 9.0;Schr\u00f6dinger, LLC:New York, NY, 2007."},{"key":"ref43\/cit43","doi-asserted-by":"crossref","first-page":"11225","DOI":"10.1021\/ja9621760","volume":"118","author":"Jorgensen W. L.","year":"1996","journal-title":"J. Am. Chem. Soc."},{"key":"ref44\/cit44","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1023\/A:1007996124545","volume":"11","author":"Eldridge M. D.","year":"1997","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref45\/cit45","doi-asserted-by":"crossref","first-page":"6472","DOI":"10.1021\/j100194a068","volume":"96","author":"Nemethy G.","year":"1992","journal-title":"J. Phys. Chem."},{"key":"ref46\/cit46","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1002\/(SICI)1096-987X(199604)17:5\/6<616::AID-JCC5>3.0.CO;2-X","volume":"17","author":"Halgren T. A.","year":"1996","journal-title":"J. Comput. Chem."},{"key":"ref47\/cit47","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1006\/jmbi.1994.1052","volume":"235","author":"Abagyan R.","year":"1994","journal-title":"J. Mol. Biol."},{"key":"ref48\/cit48","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1063\/1.1699114","volume":"21","author":"Metropolis N.","year":"1953","journal-title":"J. Chem. Phys."},{"key":"ref49\/cit49","unstructured":"SYBYL, version 7.3;Tripos Inc.:St Louis, MO."},{"key":"ref50\/cit50","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/BF00124474","volume":"10","author":"Jain A. N.","year":"1996","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref51\/cit51","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s10822-007-9114-2","volume":"21","author":"Jain A.","year":"2007","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref52\/cit52","doi-asserted-by":"crossref","first-page":"6474","DOI":"10.1021\/jp003919d","volume":"105","author":"Kaminski G. A.","year":"2001","journal-title":"J. Phys. Chem. B"},{"key":"ref53\/cit53","unstructured":"Desmond Molecular Dynamics System, version 2.2;D. E. Shaw Research, Schr\u00f6dinger, LLC:New York, NY, 2009."},{"key":"ref54\/cit54","doi-asserted-by":"crossref","unstructured":"Bowers, K. J.; Chow, E.; Xu, H.; Dror, R. O.; Eastwood, M. P.; Gregersen, B. A.; Klepeis, J. L.; Kolossvary, I.; Moraes, M. A.; Sacerdoti, F. D.; Salmon, J. K.; Shan, Y.; Shaw, D. E.InProceedings of the 2006 ACM\/IEEE conference on Supercomputing;ACM:Tampa, FL, 2006; p84.","DOI":"10.1145\/1188455.1188544"},{"key":"ref55\/cit55","volume-title":"MacroModel","year":"2007"},{"key":"ref56\/cit56","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","volume":"14","author":"Humphrey W.","year":"1996","journal-title":"J. Mol. Graph."},{"key":"ref57\/cit57","unstructured":"QSite, version 5.5;Schr\u00f6dinger, LLC:New York, NY, 2009."},{"key":"ref58\/cit58","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1021\/ja046553h","volume":"127","author":"Soriano A.","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref59\/cit59","doi-asserted-by":"crossref","first-page":"7477","DOI":"10.1021\/ja801156y","volume":"130","author":"Ruiz-Pernia J. J.","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref60\/cit60","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1073\/pnas.0711741105","volume":"105","author":"Tsai J.","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"ref61\/cit61","doi-asserted-by":"crossref","first-page":"6571","DOI":"10.1016\/j.bmcl.2009.10.030","volume":"19","author":"Wang X.","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref62\/cit62","doi-asserted-by":"crossref","first-page":"11100","DOI":"10.1158\/0008-5472.CAN-06-2554","volume":"66","author":"King A. J.","year":"2006","journal-title":"Cancer Res."},{"key":"ref63\/cit63","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/(SICI)1097-0134(20000215)38:3<261::AID-PROT3>3.0.CO;2-Q","volume":"38","author":"Garc\u00eda A. E.","year":"2000","journal-title":"Proteins"}],"container-title":["Journal of Chemical Information and Modeling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/ci100049h","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T17:33:26Z","timestamp":1740159206000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/doi\/10.1021\/ci100049h"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6,4]]},"references-count":63,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2010,6,28]]}},"alternative-id":["10.1021\/ci100049h"],"URL":"https:\/\/doi.org\/10.1021\/ci100049h","relation":{},"ISSN":["1549-9596","1549-960X"],"issn-type":[{"value":"1549-9596","type":"print"},{"value":"1549-960X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6,4]]}}}