{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:21:55Z","timestamp":1789204915715,"version":"build-2803163510"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"2","funder":[{"DOI":"10.13039\/100000139","name":"U.S. Environmental Protection Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006379","name":"Office of Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006379","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1845336"],"award-info":[{"award-number":["1845336"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Predictive toxicology is increasingly reliant on innovative computational methods to address pressing questions in chemicals assessment. Of importance is the evaluation of contaminant impact differences across species to inform ecosystem protection and identify appropriate model species for human toxicity studies. Here we evaluated 2 complementary tools to predict cross-species differences in binding affinity between per- and polyfluoroalkyl substances (PFAS) and the liver fatty acid-binding protein (LFABP): the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool and molecular dynamics (MD). SeqAPASS determined that the structure of human LFABP, a key determinant of PFAS bioaccumulation, was conserved in the majority of vertebrate species, indicating these species would have similar PFAS bioaccumulation potentials. Level 3 SeqAPASS evaluation identified several potentially destabilizing amino acid differences across species, which were generally supported by DUET stability change predictions. Nine single-residue mutations and 7 whole species sequences were selected for MD evaluation. One mutation (F50V for PFNA) showed a statistically significant difference with stronger affinity than wild-type human LFABP. Predicted binding affinities for 9 different PFAS across 7 species showed human, rat, chicken, and rainbow trout had similar binding affinities to one another for each PFAS, whereas Japanese medaka and fathead minnow had significantly weaker LFABP-binding affinity for some PFAS. Based on these analyses, the combined use of SeqAPASS and MD provides rapid screening for potential species differences with deeper structural insight. This approach can be easily extended to other important biological receptors and potential ligands.<\/jats:p>","DOI":"10.1093\/toxsci\/kfab004","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T09:04:51Z","timestamp":1610528691000},"page":"212-223","source":"Crossref","is-referenced-by-count":47,"title":["Integrative Computational Approaches to Inform Relative Bioaccumulation Potential of Per- and Polyfluoroalkyl Substances Across Species"],"prefix":"10.1093","volume":"180","author":[{"given":"Weixiao","family":"Cheng","sequence":"first","affiliation":[{"name":"Civil and Environmental Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon A","family":"Doering","sequence":"additional","affiliation":[{"name":"National Research Council, U.S. Environmental Protection Agency, Duluth, Minnesota 55804, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlie","family":"LaLone","sequence":"additional","affiliation":[{"name":"Great Lakes Toxicology and Ecology Division, Center for Computational Toxicology and Exposure, Office of Research and Development, U.S. Environmental Protection Agency, Duluth, Minnesota 55804, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5521-7862","authenticated-orcid":false,"given":"Carla","family":"Ng","sequence":"additional","affiliation":[{"name":"Civil and Environmental Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA"},{"name":"Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,1,23]]},"reference":[{"key":"2021041221224894500_kfab004-B1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.reprotox.2011.11.005","article-title":"Effects of perfluorooctanoic acid (PFOA) on expression of peroxisome proliferator-activated receptors (PPAR) and nuclear receptor-regulated genes in fetal and postnatal cd-1 mouse tissues","volume":"33","author":"Abbott","year":"2012","journal-title":"Reprod. 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