{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T07:14:22Z","timestamp":1775027662026,"version":"3.50.1"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM108889"],"award-info":[{"award-number":["R01GM108889"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM132386"],"award-info":[{"award-number":["R01GM132386"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Comput Aided Mol Des"],"published-print":{"date-parts":[[2021,3]]},"DOI":"10.1007\/s10822-020-00367-1","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T03:25:56Z","timestamp":1611804356000},"page":"271-284","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Improving small molecule force fields by identifying and characterizing small molecules with inconsistent parameters"],"prefix":"10.1007","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0150-082X","authenticated-orcid":false,"given":"Jordan N.","family":"Ehrman","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4030-9312","authenticated-orcid":false,"given":"Victoria T.","family":"Lim","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2777-1174","authenticated-orcid":false,"given":"Caitlin C.","family":"Bannan","sequence":"additional","affiliation":[]},{"given":"Nam","family":"Thi","sequence":"additional","affiliation":[]},{"given":"Daisy Y.","family":"Kyu","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1083-5533","authenticated-orcid":false,"given":"David L.","family":"Mobley","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2021,1,28]]},"reference":[{"key":"367_CR1","unstructured":"Bayly C, McKay D, Truchon J (2010) An Informal AMBER Small Molecule Force Field: Parm@ Frosst. http:\/\/www.ccl.net\/cca\/data\/parm_at_Frosst\/"},{"key":"367_CR2","unstructured":"Chodera J, Qiu Y, Boothroyd S, Wang L-P, Mobley D (2019) The Open Force Field 1.0 small molecule force field, our first optimized force field (codename \u201cParsley\u201d)"},{"key":"367_CR3","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-018-0111-4","author":"P Dauber-Osguthorpe","year":"2018","unstructured":"Dauber-Osguthorpe P, Hagler AT (2018) Biomolecular force fields: where have we been, where are we now, where do we need to go and how do we get there? J Comput Aided Mol Des. https:\/\/doi.org\/10.1007\/s10822-018-0111-4","journal-title":"J Comput Aided Mol Des"},{"issue":"7","key":"367_CR4","doi-asserted-by":"publisher","first-page":"e1005659","DOI":"10.1371\/journal.pcbi.1005659","volume":"13","author":"P Eastman","year":"2017","unstructured":"Eastman P, Swails J, Chodera JD, McGibbon RT, Zhao Y, Beauchamp KA, Wang L-P, Simmonett AC, Harrigan MP, Stern CD, Wiewiora RP, Brooks BR, Pande VS (2017) OpenMM 7: rapid development of high performance algorithms for molecular dynamics. PLOS Comput Biol 13(7):e1005659","journal-title":"PLOS Comput Biol"},{"key":"367_CR5","unstructured":"eMolecules (2015) eMolecules Database Download. https:\/\/www.emolecules.com\/info\/plus\/download-database"},{"issue":"24","key":"367_CR6","doi-asserted-by":"publisher","first-page":"6438","DOI":"10.1021\/jp411529h","volume":"118","author":"CJ Fennell","year":"2014","unstructured":"Fennell CJ, Wymer KL, Mobley DL (2014) A fixed-charge model for alcohol polarization in the condensed phase, and its role in small molecule hydration. J Phys Chem B 118(24):6438\u20136446 Publisher: American Chemical Society","journal-title":"J Phys Chem B"},{"key":"367_CR7","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/s10822-018-0134-x","volume":"33","author":"AT Hagler","year":"2018","unstructured":"Hagler AT (2018) Force field development phase II: relaxation of physics-based criteria... or inclusion of more rigorous physics into the representation of molecular energetics. J Comput Aided Mol Des 33:205\u2013264","journal-title":"J Comput Aided Mol Des"},{"key":"367_CR8","unstructured":"Haider N (2020) Checkmol\/Matchmol Homepage. http:\/\/merian.pch.univie.ac.at\/~nhaider\/cheminf\/cmmm"},{"issue":"8","key":"367_CR9","doi-asserted-by":"publisher","first-page":"5079","DOI":"10.3390\/molecules15085079","volume":"15","author":"N Haider","year":"2010","unstructured":"Haider N (2010) Functionality pattern matching as an efficient complementary structure\/reaction search tool: an open-source approach. Molecules 15(8):5079\u20135092","journal-title":"Molecules"},{"issue":"20","key":"367_CR10","doi-asserted-by":"publisher","first-page":"7827","DOI":"10.1021\/ja00046a032","volume":"114","author":"TA Halgren","year":"1992","unstructured":"Halgren TA (1992) The representation of van der Waals (vdW) interactions in molecular mechanics force fields: Potential form, combination rules, and vdW parameters. J Am Chem Soc 114(20):7827\u20137843","journal-title":"J Am Chem Soc"},{"issue":"5\u20136","key":"367_CR11","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1002\/(SICI)1096-987X(199604)17:5\/6<490::AID-JCC1>3.0.CO;2-P","volume":"17","author":"TA Halgren","year":"1996","unstructured":"Halgren TA (1996a) Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. J Comput Chem 17(5\u20136):490\u2013519","journal-title":"J Comput Chem"},{"issue":"5\u20136","key":"367_CR12","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1002\/(SICI)1096-987X(199604)17:5\/6<520::AID-JCC2>3.0.CO;2-W","volume":"17","author":"TA Halgren","year":"1996","unstructured":"Halgren TA (1996b) Merck molecular force field. II. MMFF94 van der Waals and electrostatic parameters for intermolecular interactions. J Comput Chem 17(5\u20136):520\u2013552","journal-title":"J Comput Chem"},{"issue":"5\u20136","key":"367_CR13","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1002\/(SICI)1096-987X(199604)17:5\/6<553::AID-JCC3>3.0.CO;2-T","volume":"17","author":"TA Halgren","year":"1996","unstructured":"Halgren TA (1996c) Merck molecular force field. III. Molecular geometries and vibrational frequencies for MMFF94. J Comput Chem 17(5\u20136):553\u2013586","journal-title":"J Comput Chem"},{"issue":"5\u20136","key":"367_CR14","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1002\/(SICI)1096-987X(199604)17:5\/6<616::AID-JCC5>3.0.CO;2-X","volume":"17","author":"TA Halgren","year":"1996","unstructured":"Halgren TA (1996d) Merck molecular force field. V. Extension of MMFF94 using experimental data, additional computational data, and empirical rules. J Comput Chem 17(5\u20136):616\u2013641","journal-title":"J Comput Chem"},{"issue":"7","key":"367_CR15","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1002\/(SICI)1096-987X(199905)20:7<720::AID-JCC7>3.0.CO;2-X","volume":"20","author":"TA Halgren","year":"1999","unstructured":"Halgren TA (1999) MMFF VI. MMFF94s option for energy minimization studies. J Comput Chem 20(7):720\u2013729","journal-title":"J Comput Chem"},{"issue":"5\u20136","key":"367_CR16","first-page":"587","volume":"17","author":"TA Halgren","year":"1996","unstructured":"Halgren TA, Nachbar RB (1996) Merck molecular force field. IV. conformational energies and geometries for MMFF94. J Comput Chem 17(5\u20136):587\u2013615","journal-title":"J Comput Chem"},{"issue":"1","key":"367_CR17","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1021\/acs.jctc.5b00864","volume":"12","author":"E Harder","year":"2016","unstructured":"Harder E, Damm W, Maple J, Wu C, Reboul M, Xiang JY, Wang L, Lupyan D, Dahlgren MK, Knight JL, Kaus JW, Cerutti DS, Krilov G, Jorgensen WL, Abel R, Friesner RA (2016) OPLS3: a force field providing broad coverage of drug-like small molecules and proteins. J Chem Theory Comput 12(1):281\u2013296","journal-title":"J Chem Theory Comput"},{"issue":"4","key":"367_CR18","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1021\/ci100031x","volume":"50","author":"PCD Hawkins","year":"2010","unstructured":"Hawkins PCD, Skillman AG, Warren GL, Ellingson BA, Stahl MT (2010) Conformer generation with OMEGA: algorithm and validation using high quality structures from the protein databank and Cambridge structural database. J Chem Inf Model 50(4):572\u2013584","journal-title":"J Chem Inf Model"},{"issue":"2","key":"367_CR19","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1002\/(SICI)1096-987X(20000130)21:2<132::AID-JCC5>3.0.CO;2-P","volume":"21","author":"A Jakalian","year":"2000","unstructured":"Jakalian A, Bush BL, Jack DB, Bayly CI (2000) Fast, efficient generation of high-quality atomic charges. AM1-BCC model: I. Method. J Comput Chem 21(2):132\u2013146","journal-title":"J Comput Chem"},{"issue":"16","key":"367_CR20","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1002\/jcc.10128","volume":"23","author":"A Jakalian","year":"2002","unstructured":"Jakalian A, Jack DB, Bayly CI (2002) Fast, efficient generation of high-quality atomic charges. AM1-BCC model: II. Parameterization and validation. J Comput Chem 23(16):1623\u20131641","journal-title":"J Comput Chem"},{"key":"367_CR21","unstructured":"Jang H (2020) Update on Parsley minor releases (openff-1.1.0, 1.2.0)"},{"key":"367_CR22","unstructured":"Jang H, Maat J, Qiu Y, Smith DG, Boothroyd S, Wagner J, Bannan CC, Gokey T, Lim VT, Lucas X, Tjanaka B, Shirts MR, Gilson MK, Chodera JD, Bayly CI, Mobley DL, Wang L-P (2020) Openforcefield\/openforcefields: Version 1.2.0 \u201cParsley\u201d Update. Zenodo"},{"issue":"2","key":"367_CR23","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1063\/1.445869","volume":"79","author":"WL Jorgensen","year":"1983","unstructured":"Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79(2):926\u2013935","journal-title":"J Chem Phys"},{"key":"367_CR24","doi-asserted-by":"crossref","unstructured":"Lim VT, Hahn DF, Tresadern G, Bayly CI, Mobley D (2020) Benchmark assessment of molecular geometries and energies from small molecule force fields. chemRxiv","DOI":"10.26434\/chemrxiv.12551867.v2"},{"key":"367_CR25","unstructured":"Maat J (2020) Training dataset selection"},{"key":"367_CR26","doi-asserted-by":"crossref","unstructured":"Mobley DL, Bannan CC, Rizzi A, Bayly CI, Chodera JD, Lim VT, Lim NM, Beauchamp KA, Shirts MR, Gilson MK, Eastman PK (2018a) Open Force Field Consortium: escaping atom types using direct chemical perception with SMIRNOFF v0.1. bioRxiv, p. 286542","DOI":"10.1101\/286542"},{"key":"367_CR27","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1021\/acs.jctc.8b00640","volume":"14","author":"DL Mobley","year":"2018","unstructured":"Mobley DL, Bannan CC, Rizzi A, Bayly CI, Chodera JD, Lim VT, Lim NM, Beauchamp KA, Slochower DR, Shirts MR, Gilson MK, Eastman PK (2018b) Escaping atom types in force fields using direct chemical perception. J Chem Theory Comput 14:11","journal-title":"J Chem Theory Comput"},{"issue":"3","key":"367_CR28","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1137\/0801023","volume":"1","author":"SG Nash","year":"1991","unstructured":"Nash SG, Nocedal J (1991) A numerical study of the limited memory BFGS method and the truncated-Newton method for large scale optimization. SIAM J Optim 1(3):358\u2013372","journal-title":"SIAM J Optim"},{"key":"367_CR29","unstructured":"Qiu Y, Smith DGA, Boothroyd S, Wagner J, Bannan CC,Gokey T, Jang H, Lim VT, Stern CD, Rizzi A, Lucas X,Tjanaka B, Shirts MR, Gilson MK, Chodera JD, BaylyCI, Mobley DL, Wang L-P (2019) Introducing the firstoptimized Open Force Field 1.0.0 (codename \u201dParsley\u201d)"},{"issue":"3","key":"367_CR30","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.1021\/acs.jctc.8b01026","volume":"15","author":"K Roos","year":"2019","unstructured":"Roos K, Wu C, Damm W, Reboul M, Stevenson JM, Lu C, Dahlgren MK, Mondal S, Chen W, Wang L, Abel R, Friesner RA, Harder ED (2019) OPLS3e: extending force field coverage for drug-like small molecules. J Chem Theory Comput 15(3):1863\u20131874","journal-title":"J Chem Theory Comput"},{"issue":"6","key":"367_CR31","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1021\/ci2002318","volume":"52","author":"T Schulz-Gasch","year":"2012","unstructured":"Schulz-Gasch T, Sch\u00e4rfer C, Guba W, Rarey M (2012a) TFD: Torsion Fingerprints as a new measure to compare small molecule conformations. J Chem Inf Model 52(6):1499\u20131512","journal-title":"J Chem Inf Model"},{"issue":"6","key":"367_CR32","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1021\/ci2002318","volume":"52","author":"T Schulz-Gasch","year":"2012","unstructured":"Schulz-Gasch T, Sch\u00e4rfer C, Guba W, Rarey M (2012b) TFD: Torsion Fingerprints as a new measure to compare small molecule conformations. J Chem Inf Model 52(6):1499\u20131512","journal-title":"J Chem Inf Model"},{"issue":"6","key":"367_CR33","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1021\/acs.jcim.6b00614","volume":"57","author":"BD Sellers","year":"2017","unstructured":"Sellers BD, James NC, Gobbi A (2017) A comparison of quantum and molecular mechanical methods to estimate strain energy in drug like fragments. J Chem Inf Model 57(6):1265\u20131275","journal-title":"J Chem Inf Model"},{"key":"367_CR34","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1491","author":"DGA Smith","year":"2020","unstructured":"Smith DGA, Altarawy D, Burns LA, Welborn M, Naden LN, Ward L, Ellis S, Pritchard BP, Crawford TD (2020) The MolSSI QCArchive project: an open-source platform to compute, organize, and share quantum chemistry data. WIREs Comput Mol Sci. https:\/\/doi.org\/10.1002\/wcms.1491","journal-title":"WIREs Comput Mol Sci"},{"key":"367_CR35","volume-title":"Version 1.9.0","author":"Szybki ToolKit","year":"2015","unstructured":"ToolKit Szybki (2015) Version 1.9.0. OpenEye Scientific Software Inc., Santa Fe"},{"issue":"12","key":"367_CR36","doi-asserted-by":"publisher","first-page":"3144","DOI":"10.1021\/ci300363c","volume":"52","author":"K Vanommeslaeghe","year":"2012","unstructured":"Vanommeslaeghe K, MacKerell AD (2012) Automation of the CHARMM General Force Field (CGenFF) I: bond perception and atom typing. J Chem Inf Model 52(12):3144\u20133154","journal-title":"J Chem Inf Model"},{"issue":"12","key":"367_CR37","doi-asserted-by":"publisher","first-page":"3155","DOI":"10.1021\/ci3003649","volume":"52","author":"K Vanommeslaeghe","year":"2012","unstructured":"Vanommeslaeghe K, Raman EP, MacKerell AD (2012) Automation of the CHARMM General Force Field (CGenFF) II: assignment of bonded parameters and partial atomic charges. J Chem Inf Model 52(12):3155\u20133168","journal-title":"J Chem Inf Model"},{"key":"367_CR38","unstructured":"Wagner J (2020) Openforcefield\/openforcefields: Version 1.1.0 \u201cParsley\u201d Update. Zenodo"},{"key":"367_CR39","unstructured":"Wang J (2017) A snapshot of GAFF2 development"},{"issue":"9","key":"367_CR40","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1002\/jcc.20035","volume":"25","author":"J Wang","year":"2004","unstructured":"Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA (2004) Development and testing of a general amber force field. J Comput Chem 25(9):1157\u20131174","journal-title":"J Comput Chem"},{"issue":"2","key":"367_CR41","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.jmgm.2005.12.005","volume":"25","author":"J Wang","year":"2006","unstructured":"Wang J, Wang W, Kollman PA, Case DA (2006) Automatic atom type and bond type perception in molecular mechanical calculations. J Mol Graph Model 25(2):247\u2013260","journal-title":"J Mol Graph Model"},{"issue":"7","key":"367_CR42","doi-asserted-by":"publisher","first-page":"2140","DOI":"10.1021\/ct100095p","volume":"6","author":"S Wlodek","year":"2010","unstructured":"Wlodek S, Skillman A, Nicholls A (2010) Ligand entropy in gas-phase, upon solvation and protein complexation. fast estimation with quasi-Newton Hessian. J Chem Theory Comput 6(7):2140\u20132152","journal-title":"J Chem Theory Comput"}],"container-title":["Journal of Computer-Aided Molecular Design"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10822-020-00367-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10822-020-00367-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10822-020-00367-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,21]],"date-time":"2021-03-21T23:05:18Z","timestamp":1616367918000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s10822-020-00367-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,28]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["367"],"URL":"https:\/\/doi.org\/10.1007\/s10822-020-00367-1","relation":{"has-preprint":[{"id-type":"doi","id":"10.26434\/chemrxiv.12846602","asserted-by":"object"},{"id-type":"doi","id":"10.26434\/chemrxiv.12846602.v1","asserted-by":"object"}]},"ISSN":["0920-654X","1573-4951"],"issn-type":[{"value":"0920-654X","type":"print"},{"value":"1573-4951","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,28]]},"assertion":[{"value":"10 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"We provide the code used in this project in our GitHub repository (\n                      \n                      and with a DOI at\n                      \n                      ). Additionally, at\n                      \n                      we provide a supporting data package. This includes a .csv file which has TanimotoCombo and TFD scores, SMILES strings, and eMolecules identifiers for all 2,698,456 molecules analyzed. Additionally, we provide optimized geometries of 265,847 molecules with four or more difference flags. An archived copy of the GitHub repository is provided in the electronic Supporting Information associated with this paper.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Code and data availability"}},{"value":"The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclaimers"}},{"value":"DLM is a member of the Scientific Advisory Board of OpenEye Scientific Software and an Open Science Fellow with Silicon Therapeutics.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclosures"}}]}}