{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T16:01:49Z","timestamp":1775491309689,"version":"3.50.1"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2016,10,8]],"date-time":"2016-10-08T00:00:00Z","timestamp":1475884800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"name":"Deanship of Scientific Research, Jordan University, amman, jordan"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Comput Aided Mol Des"],"published-print":{"date-parts":[[2016,12]]},"DOI":"10.1007\/s10822-016-9984-2","type":"journal-article","created":{"date-parts":[[2016,10,8]],"date-time":"2016-10-08T13:27:57Z","timestamp":1475933277000},"page":"1149-1163","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Combining molecular dynamics simulation and ligand-receptor contacts analysis as a new approach for pharmacophore modeling: beta-secretase 1 and check point kinase 1 as case studies"],"prefix":"10.1007","volume":"30","author":[{"given":"Ma\u2019mon M.","family":"Hatmal","sequence":"first","affiliation":[]},{"given":"Shadi","family":"Jaber","sequence":"additional","affiliation":[]},{"given":"Mutasem O.","family":"Taha","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2016,10,8]]},"reference":[{"key":"9984_CR1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s00894-010-0701-0","volume":"17","author":"BV Kumar","year":"2011","unstructured":"Kumar BV, Kotla R, Buddiga R et al (2011) Ligand-based and structure-based approaches in identifying ideal pharmacophore against c-Jun N-terminal kinase-3. J Mol Model 17:151\u2013163","journal-title":"J Mol Model"},{"key":"9984_CR2","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.2174\/0929867013372481","volume":"8","author":"Y Kurogi","year":"2001","unstructured":"Kurogi Y, G\u00fcner O (2001) Pharmacophore modeling and three dimensional database searching for drug design using catalyst. Curr Med Chem 8:1035\u20131055","journal-title":"Curr Med Chem"},{"key":"9984_CR3","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1007\/s10822-013-9699-6","volume":"27","author":"S Abuhamdah","year":"2013","unstructured":"Abuhamdah S, Habash M, Taha MO (2013) Elaborate ligand-based modeling coupled with QSAR analysis and in silico screening reveal new potent acetylcholinesterase inhibitors. J Comput Aided Mol Des 27:1075\u20131092","journal-title":"J Comput Aided Mol Des"},{"key":"9984_CR4","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.jmgm.2011.02.001","volume":"29","author":"AH Al-Nadaf","year":"2011","unstructured":"Al-Nadaf AH, Taha MO (2011) Discovery of new renin inhibitory leads via sequential pharmacophore modeling, QSAR analysis, in silico screening and in vitro evaluation. J Mol Graph Model 29:843\u2013864","journal-title":"J Mol Graph Model"},{"key":"9984_CR5","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jmgm.2013.03.003","volume":"42","author":"MA Al-Sha\u2019er","year":"2013","unstructured":"Al-Sha\u2019er MA, Vanpatten S, Al-Abed Y, Taha MO (2013) Elaborate ligand-based modeling reveal new migration inhibitory factor inhibitors. J Mol Graph Model 42:104\u2013114","journal-title":"J Mol Graph Model"},{"key":"9984_CR6","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1007\/s00894-014-2080-4","volume":"20","author":"MA Al-Sha\u2019er","year":"2014","unstructured":"Al-Sha\u2019er MA, Khanfar MA, Taha MO (2014) Discovery of novel urokinase plasminogen activator (uPA) inhibitors using ligand-based modeling and virtual screening followed by in vitro analysis. J Mol Model 20:2080\u20132084","journal-title":"J Mol Model"},{"key":"9984_CR7","doi-asserted-by":"crossref","first-page":"3876","DOI":"10.1007\/s00044-014-0966-4","volume":"23","author":"M Habash","year":"2014","unstructured":"Habash M, Abdelazeem AH, Taha MO (2014) Elaborate ligand-based modeling reveals new human neutrophil elastase inhibitors. Med Chem Res 23:3876\u20133896","journal-title":"Med Chem Res"},{"key":"9984_CR8","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jmgm.2013.02.009","volume":"42","author":"MA Khanfar","year":"2013","unstructured":"Khanfar MA, Abukhader MM, Alqtaishat S, Taha MO (2013) Pharmacophore modeling, homology modeling, and in silico screening reveal mammalian target of rapamycin inhibitory activities for sotalol, glyburide, metipranolol, sulfamethizole, glipizide, and pioglitazone. J Mol Graph Model 42:39\u201349","journal-title":"J Mol Graph Model"},{"key":"9984_CR9","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.bmc.2011.10.071","volume":"20","author":"R Shahin","year":"2012","unstructured":"Shahin R, Taha MO (2012) Elaborate ligand-based modeling and subsequent synthetic exploration unveil new nanomolar Ca2+\/calmodulin-dependent protein kinase II inhibitory leads. Bioorg Med Chem 20:377\u2013400","journal-title":"Bioorg Med Chem"},{"key":"9984_CR10","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s10822-011-9509-y","volume":"26","author":"R Shahin","year":"2012","unstructured":"Shahin R, Alqtaishat S, Taha MO (2012) Elaborate ligand-based modeling reveal new submicromolar Rho kinase inhibitors. J Comput Aided Mol Des 26:249\u2013266","journal-title":"J Comput Aided Mol Des"},{"key":"9984_CR11","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/j.1747-0285.2011.01160.x","volume":"78","author":"MO Taha","year":"2011","unstructured":"Taha MO, Qandil AM, Al-Haraznah T et al (2011) Discovery of new antifungal leads via pharmacophore modeling and QSAR analysis of fungal N-myristoyl transferase inhibitors followed by in silico screening. Chem Biol Drug Des 78:391\u2013407","journal-title":"Chem Biol Drug Des"},{"key":"9984_CR12","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jmgm.2014.12.003","volume":"56","author":"MO Taha","year":"2014","unstructured":"Taha MO, Habash M, Hatmal MM, Abdelazeem AH, Qandil A (2014) Ligand-based modeling followed by in vitro bioassay yielded new potent glucokinase activators. J Mol Graph Model 56:91\u2013102","journal-title":"J Mol Graph Model"},{"key":"9984_CR13","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/9783527613168.ch3","volume":"8","author":"GM Morris","year":"2000","unstructured":"Morris GM, Olson AJ, Goodsell DS (2000) Protein-ligand docking methods. Princ Med Chem 8:31\u201348","journal-title":"Princ Med Chem"},{"key":"9984_CR14","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1016\/j.jmgm.2006.08.008","volume":"25","author":"MO Taha","year":"2007","unstructured":"Taha MO, Bustanji Y, Al-Bakri AG et al (2007) Discovery of new potent human protein tyrosine phosphatase inhibitors via pharmacophore and QSAR analysis followed by in silico screening. J Mol Graph Model 25:870\u2013884","journal-title":"J Mol Graph Model"},{"issue":"22","key":"9984_CR15","doi-asserted-by":"crossref","first-page":"5902","DOI":"10.1016\/j.bmcl.2006.08.069","volume":"16","author":"MO Taha","year":"2006","unstructured":"Taha MO, Al-Bakri AG, Zalloum WA (2006) Discovery of potent inhibitors of pseudomonal quorum sensing via pharmacophore modeling and in silico screening. Bioorg Med Chem Lett 16(22):5902\u20135906","journal-title":"Bioorg Med Chem Lett"},{"key":"9984_CR16","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1021\/jm0302997","volume":"47","author":"M Kontoyianni","year":"2004","unstructured":"Kontoyianni M, McClellan LM, Sokol GS (2004) Evaluation of docking performance: comparative data on docking algorithms. J Med Chem 47:558\u2013565","journal-title":"J Med Chem"},{"key":"9984_CR17","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1517\/17460441003713462","volume":"5","author":"C Beier","year":"2010","unstructured":"Beier C, Zacharias M (2010) Tackling the challenges posed by target flexibility in drug design. Expert Opin Drug Discov 5:347\u2013359","journal-title":"Expert Opin Drug Discov"},{"key":"9984_CR18","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1517\/17460441.1.3.261","volume":"1","author":"T Langer","year":"2006","unstructured":"Langer T, Hoffmann RD (2006) Pharmacophore modelling: applications in drug discovery. Expert Opin Drug Discov 1:261\u2013267","journal-title":"Expert Opin Drug Discov"},{"key":"9984_CR19","doi-asserted-by":"crossref","first-page":"4843","DOI":"10.1007\/s00894-012-1479-z","volume":"18","author":"MA Al-Sha\u2019er","year":"2012","unstructured":"Al-Sha\u2019er MA, Taha MO (2012) Application of docking-based comparative intermolecular contacts analysis for validating Hsp90\u03b1 docking studies and subsequent in silico screening for inhibitors. J Mol Model 18:4843\u20134863","journal-title":"J Mol Model"},{"key":"9984_CR20","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1021\/ci100368t","volume":"51","author":"MO Taha","year":"2011","unstructured":"Taha MO, Habash M, Al-Hadidi Z et al (2011) Docking-based comparative intermolecular contacts analysis as new 3D QSAR concept for validating docking studies and in silico screening: NMT and GP inhibitors as case studies. J Chem Inf Model 51:647\u2013669","journal-title":"J Chem Inf Model"},{"key":"9984_CR21","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s10822-014-9740-4","volume":"28","author":"MO Taha","year":"2014","unstructured":"Taha MO, Habash M, Khanfar MA (2014) The use of docking-based comparative intermolecular contacts analysis to identify optimal docking conditions within glucokinase and to discover of new GK activators. J Comput Aided Mol Des 28:509\u2013547","journal-title":"J Comput Aided Mol Des"},{"key":"9984_CR22","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1039\/C1MD00210D","volume":"3","author":"MPA Sanders","year":"2012","unstructured":"Sanders MPA, McGuire R, Roumen L et al (2012) From the protein\u2019s perspective: the benefits and challenges of protein structure-based pharmacophore modeling. Med Chem Commun 3:28\u201338","journal-title":"Med Chem Commun"},{"key":"9984_CR23","doi-asserted-by":"crossref","DOI":"10.1002\/3527609164.ch15","volume-title":"Are you sure you have a good model?","author":"N Triballeau","year":"2006","unstructured":"Triballeau N, Bertrand HO, Acher F (2006) Methods and principles in medicinal chemistry-pharmacophores and pharmacophore searches. In: Langer T, Hoffmann RD (eds) Are you sure you have a good model? Wiley-VCH, Weinheim"},{"key":"9984_CR24","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1002\/anie.200802019","volume":"48","author":"HM Senn","year":"2009","unstructured":"Senn HM, Thiel W (2009) QM\/MM methods for biomolecular systems. Angew Chem (Int Ed) 48:1198\u20131229","journal-title":"Angew Chem (Int Ed)"},{"key":"9984_CR25","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/prot.340230111","volume":"23","author":"JM Troyer","year":"2015","unstructured":"Troyer JM, Cohen FE (2015) Protein conformational landscapes: energy minimization and clustering of a long molecular dynamics trajectory. Proteins 23:97\u2013110","journal-title":"Proteins"},{"key":"9984_CR26","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1021\/acs.jctc.5b00003","volume":"11","author":"GSC Mauricio","year":"2015","unstructured":"Mauricio GSC, Batista PR, Bisch PM, Perahia D (2015) Exploring free energy landscapes of large conformational changes: molecular dynamics with excited normal modes. J Chem Theory Comput 11:2755\u20132767","journal-title":"J Chem Theory Comput"},{"key":"9984_CR27","doi-asserted-by":"crossref","first-page":"e97975","DOI":"10.1371\/journal.pone.0097975","volume":"9","author":"C Eun","year":"2014","unstructured":"Eun C, Ortiz-S\u00e1nchez JM, Da L et al (2014) Molecular dynamics simulation study of conformational changes of transcription factor TFIIS during RNA polymerase II transcriptional arrest and reactivation. PLoS One 9:e97975","journal-title":"PLoS One"},{"key":"9984_CR28","doi-asserted-by":"crossref","first-page":"4968","DOI":"10.1063\/1.474860","volume":"107","author":"WK Otter Den","year":"1997","unstructured":"Den Otter WK, Briels WJ (1997) Molecular dynamics simulations of free energy and conformational transition rates of calix[4]arene in chloroform. J Chem Phys 107:4968","journal-title":"J Chem Phys"},{"key":"9984_CR29","doi-asserted-by":"crossref","first-page":"e1003366","DOI":"10.1371\/journal.pcbi.1003366","volume":"9","author":"AO Aykut","year":"2013","unstructured":"Aykut AO, Atilgan AR, Atilgan C (2013) designing molecular dynamics simulations to shift populations of the conformational states of calmodulin. PLoS Comput Biol 9:e1003366","journal-title":"PLoS Comput Biol"},{"key":"9984_CR30","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1023\/B:JCAM.0000022559.72848.1c","volume":"18","author":"M Pinto","year":"2004","unstructured":"Pinto M, Perez JJ, Rubio-Martinez JJ (2004) Molecular dynamics\u00a0study of peptide segments of the BH3 domain of the proapoptotic proteins Bak, Bax, Bid and Hrk bound to the Bcl-xL and Bcl-2 proteins. Comput Aided Mol Des 18:13\u201322","journal-title":"Comput Aided Mol Des"},{"key":"9984_CR31","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1021\/jm990322h","volume":"43","author":"A Heather","year":"2000","unstructured":"Heather A, Carlson HA, Masukawa KM et al (2000) Developing a dynamic pharmacophore model for HIV-1 integrase. J Med Chem 43:2100\u20132114","journal-title":"J Med Chem"},{"key":"9984_CR32","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1080\/07391102.2014.908142","volume":"33","author":"SP Kumar","year":"2015","unstructured":"Kumar SP, Jasrai YT, Mehta VP, Pandya HA (2015) Development of pharmacophore similarity-based quantitative activity hypothesis and its applicability domain: applied on a diverse data-set of HIV-1 integrase inhibitors. J Biomol Struct Dyn 33:706\u2013722","journal-title":"J Biomol Struct Dyn"},{"key":"9984_CR33","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1021\/acs.jcim.5b00169","volume":"55","author":"F Spyrakis","year":"2015","unstructured":"Spyrakis F, Benedetti P, Decherchi S et al (2015) A pipeline to enhance ligand virtual screening: integrating molecular dynamics and FLAP. J Chem Inf Model 55:2256\u20132274","journal-title":"J Chem Inf Model"},{"key":"9984_CR34","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1021\/ci300154n","volume":"52","author":"S Cross","year":"2012","unstructured":"Cross S, Ortuso F, Baroni M et al (2012) GRID-based\u00a0three-dimensional\u00a0pharmacophores\u00a0II:\u00a0PharmBench, a\u00a0benchmark\u00a0data\u00a0set for\u00a0evaluating\u00a0pharmacophore\u00a0elucidation\u00a0methods. J Chem Inf Model 52:2599\u20132608","journal-title":"J Chem Inf Model"},{"key":"9984_CR35","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1021\/acs.jcim.5b00336","volume":"55","author":"F Shirgahi Talari","year":"2015","unstructured":"Shirgahi Talari F, Bagherzadeh K, Golestanian S et al (2015) Potent\u00a0human\u00a0telomerase\u00a0inhibitors:\u00a0molecular\u00a0dynamic\u00a0simulations,\u00a0multiplepharmacophore-based\u00a0virtual\u00a0screening, and\u00a0biochemical\u00a0assays. J Chem Inf Model 55:2596\u20132610","journal-title":"J Chem Inf Model"},{"key":"9984_CR36","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1021\/ci4006657","volume":"54","author":"B Lai","year":"2014","unstructured":"Lai B, Nagy G, Garate JA, Oostenbrink C (2014) Entropic and enthalpic contributions to stereospecific ligand binding from enhanced sampling methods. J Chem Inf Model 54:151\u2013158","journal-title":"J Chem Inf Model"},{"key":"9984_CR37","doi-asserted-by":"crossref","first-page":"6960","DOI":"10.1021\/acs.jmedchem.5b00812","volume":"58","author":"E R\u00fchmann","year":"2014","unstructured":"R\u00fchmann E, Betz M, Heine A, Klebe G (2014) Fragment binding can be either more enthalpy-driven or entropy-driven: crystal structures and residual hydration patterns suggest why. J Med Chem 58:6960\u20136971","journal-title":"J Med Chem"},{"key":"9984_CR38","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.dnarep.2004.03.001","volume":"3","author":"CC Chini","year":"2004","unstructured":"Chini CC, Chen J (2004) Claspin, a regulator of Chk1 in DNA replication stress pathway. DNA Repair (Amst) 3:1033\u20131037","journal-title":"DNA Repair (Amst)"},{"key":"9984_CR39","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1126\/science.1132341","volume":"314","author":"M Willem","year":"2006","unstructured":"Willem M, Garratt AN, Novak B et al (2006) Control of peripheral nerve myelination by the beta-secretase BACE1. Science 314:664\u2013666","journal-title":"Science"},{"key":"9984_CR40","volume-title":"An introduction to hydrogen bonding","author":"GA Jeffrey","year":"1997","unstructured":"Jeffrey GA (1997) An introduction to hydrogen bonding. Oxford University Press, Oxford"},{"key":"9984_CR41","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1021\/jm049092j","volume":"48","author":"N Triballeau","year":"2005","unstructured":"Triballeau N, Acher F, Brabet I et al (2005) Virtual screening workflow development guided by the \u201creceiver operating characteristic\u201d curve approach. Application to high-throughput docking on metabotropic glutamate receptor subtype 4. J Med Chem 48:2534\u20132547","journal-title":"J Med Chem"},{"key":"9984_CR42","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.2174\/092986708785132843","volume":"15","author":"J Kirchmair","year":"2008","unstructured":"Kirchmair J, Distinto D, Schuster D et al (2008) Enhancing drug discovery through in silico screening: strategies to increase true positives retrieval rates. Curr Med Chem 15:2040\u20132053","journal-title":"Curr Med Chem"},{"key":"9984_CR43","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s10822-007-9163-6","volume":"22","author":"J Kirchmair","year":"2008","unstructured":"Kirchmair J, Markt P, Distinto S et al (2008) Evaluation of the performance of 3D virtual screening protocols: RMSD comparisons, enrichment assessments, and decoy selection\u2014what can we learn from earlier mistakes? J Comput Aided Mol Des 22:213\u2013228","journal-title":"J Comput Aided Mol Des"},{"key":"9984_CR44","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1093\/nar\/gkr777","volume":"40","author":"A Gaulton","year":"2012","unstructured":"Gaulton A, Bellis LJ, Bento AP et al (2012) ChEMBL: a large-scale bioactivity database for drug discovery. Nucleic Acids Res 40:1100\u20131107","journal-title":"Nucleic Acids Res"},{"key":"9984_CR45","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.bbrc.2016.01.081","volume":"470","author":"M Wieder","year":"2016","unstructured":"Wieder M, Perricone U, Boresch S, Seidel T, Langer T (2016) Evaluating the stability of pharmacophore features using molecular dynamic simulations. Biochem Biophys Res Commun 470:685\u2013689","journal-title":"Biochem Biophys Res Commun"},{"key":"9984_CR46","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1021\/ci500737b","volume":"55","author":"C Choudhury","year":"2015","unstructured":"Choudhury C, Priyakumar UD, Sastry GN (2015) Dynamics based pharmacophore models for screening potential inhibitors of mycobacterial cyclopropane synthase. J Chem Inf Model 55:848\u2013860","journal-title":"J Chem Inf Model"}],"container-title":["Journal of Computer-Aided Molecular Design"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10822-016-9984-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10822-016-9984-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10822-016-9984-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2017,6,25]],"date-time":"2017-06-25T00:40:31Z","timestamp":1498351231000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s10822-016-9984-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,10,8]]},"references-count":46,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["9984"],"URL":"https:\/\/doi.org\/10.1007\/s10822-016-9984-2","relation":{},"ISSN":["0920-654X","1573-4951"],"issn-type":[{"value":"0920-654X","type":"print"},{"value":"1573-4951","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,8]]}}}