{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T20:05:27Z","timestamp":1762113927116,"version":"3.37.3"},"reference-count":79,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T00:00:00Z","timestamp":1679875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NSF-GRFP","award":["DGE-1445197 and DGE-1937963"],"award-info":[{"award-number":["DGE-1445197 and DGE-1937963"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB1423, project number 421152132"],"award-info":[{"award-number":["SFB1423, project number 421152132"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH NGMS","award":["R01 GM080403"],"award-info":[{"award-number":["R01 GM080403"]}]},{"name":"NIH NIDA","award":["R01 DA046138"],"award-info":[{"award-number":["R01 DA046138"]}]},{"name":"NIH NIHL","award":["R01 HL122010"],"award-info":[{"award-number":["R01 HL122010"]}]},{"DOI":"10.13039\/100005156","name":"Alexander von Humboldt-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005156","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Lipid molecules such as cholesterol interact with the surface of integral membrane proteins (IMP) in a mode different from drug-like molecules in a protein binding pocket. These differences are due to the lipid molecule\u2019s shape, the membrane\u2019s hydrophobic environment, and the lipid\u2019s orientation in the membrane. We can use the recent increase in experimental structures in complex with cholesterol to understand protein-cholesterol interactions. We developed the RosettaCholesterol protocol consisting of (1) a prediction phase using an energy grid to sample and score native-like binding poses and (2) a specificity filter to calculate the likelihood that a cholesterol interaction site may be specific. We used a multi-pronged benchmark (self-dock, flip-dock, cross-dock, and global-dock) of protein-cholesterol complexes to validate our method. RosettaCholesterol improved sampling and scoring of native poses over the standard RosettaLigand baseline method in 91% of cases and performs better regardless of benchmark complexity. On the \u03b22AR, our method found one likely-specific site, which is described in the literature. The RosettaCholesterol protocol quantifies cholesterol binding site specificity. Our approach provides a starting point for high-throughput modeling and prediction of cholesterol binding sites for further experimental validation.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1010947","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T17:22:15Z","timestamp":1679937735000},"page":"e1010947","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Docking cholesterol to integral membrane proteins with Rosetta"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6811-9951","authenticated-orcid":true,"given":"Brennica","family":"Marlow","sequence":"first","affiliation":[]},{"given":"Georg","family":"Kuenze","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8945-193X","authenticated-orcid":true,"given":"Jens","family":"Meiler","sequence":"additional","affiliation":[]},{"given":"Julia","family":"Koehler Leman","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2023,3,27]]},"reference":[{"issue":"3","key":"pcbi.1010947.ref001","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1006\/jmbi.2000.4315","article-title":"Predicting transmembrane protein topology with a hidden markov model: application to complete genomes","volume":"305","author":"A Krogh","year":"2001","journal-title":"J Mol Biol"},{"issue":"12","key":"pcbi.1010947.ref002","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/nrd2199","article-title":"How many drug targets are there?","volume":"5","author":"JP Overington","year":"2006","journal-title":"Nature Reviews Drug Discovery"},{"issue":"9","key":"pcbi.1010947.ref003","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.tibs.2011.06.007","article-title":"Biological membranes: the importance of molecular detail","volume":"36","author":"AG Lee","year":"2011","journal-title":"Trends Biochem Sci [Internet]"},{"journal-title":"Membrane Proteins","year":"2002","author":"B Alberts","key":"pcbi.1010947.ref004"},{"journal-title":"Cell Membranes","year":"2000","author":"GM Cooper","key":"pcbi.1010947.ref005"},{"issue":"2","key":"pcbi.1010947.ref006","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/nrm2336","article-title":"Cellular cholesterol trafficking and compartmentalization","volume":"9","author":"E. Ikonen","year":"2008","journal-title":"Nat Rev Mol Cell Biol [Internet]."},{"issue":"12","key":"pcbi.1010947.ref007","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1007\/s00018-018-2789-9","article-title":"Challenges and approaches to understand cholesterol-binding impact on membrane protein function: an NMR view","volume":"75","author":"G Jaipuria","year":"2018","journal-title":"Cell Mol Life Sci [Internet]."},{"issue":"2","key":"pcbi.1010947.ref008","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1017\/S0033583500001797","article-title":"Phase transitions and fluidity characteristics of lipids and cell membranes","volume":"8","author":"D. Chapman","year":"1975","journal-title":"Q Rev Biophys [Internet]"},{"issue":"2","key":"pcbi.1010947.ref009","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/jnr.20546","article-title":"Cholesterol-dependent modulation of type 1 cannabinoid receptors in nerve cells","volume":"81","author":"M Bari","year":"2005","journal-title":"J Neurosci Res [Internet]"},{"issue":"11","key":"pcbi.1010947.ref010","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1016\/S0022-2275(20)34940-3","article-title":"Use of cyclodextrins for manipulating cellular cholesterol content","volume":"38","author":"AE Christian","year":"1997","journal-title":"J Lipid Res [Internet]"},{"issue":"1","key":"pcbi.1010947.ref011","first-page":"1","article-title":"CHIMs are versatile cholesterol analogs mimicking and visualizing cholesterol behavior in lipid bilayers and cells","volume":"4","author":"ALL Matos","year":"2021","journal-title":"Communications Biology"},{"issue":"2","key":"pcbi.1010947.ref012","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1194\/jlr.M065326","article-title":"A comparative study on fluorescent cholesterol analogs as versatile cellular reporters","volume":"57","author":"E Sezgin","year":"2016","journal-title":"J Lipid Res [Internet]"},{"issue":"12","key":"pcbi.1010947.ref013","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1007\/s00018-018-2789-9","article-title":"Challenges and approaches to understand cholesterol-binding impact on membrane protein function: an NMR view","volume":"75","author":"G Jaipuria","year":"2018","journal-title":"Cell Mol Life Sci [Internet]"},{"issue":"3","key":"pcbi.1010947.ref014","first-page":"538","article-title":"ROSETTALIGAND: Protein\u2013small molecule docking with full side-chain flexibility. Proteins: Structure, Function, and","volume":"65","author":"J Meiler","year":"2006","journal-title":"Bioinformatics [Internet]"},{"issue":"16","key":"pcbi.1010947.ref015","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated Docking with Selective Receptor Flexibility","volume":"30","author":"GM Morris","year":"2009","journal-title":"J Comput Chem [Internet]"},{"issue":"6","key":"pcbi.1010947.ref016","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1002\/jcc.20634","article-title":"A semiempirical free energy force field with charge-based desolvation","volume":"28","author":"R Huey","year":"2007","journal-title":"J Comput Chem [Internet]"},{"issue":"14","key":"pcbi.1010947.ref017","first-page":"16391662","article-title":"Automated Docking Using a Lamarckian Genetic Algorithm and an Empirical Binding Free Energy Function","volume":"19","author":"GM Morris","year":"1639","journal-title":"J Comput Chem"},{"issue":"7","key":"pcbi.1010947.ref018","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: A New Approach for Rapid, Accurate Docking and Scoring. 1. Method and Assessment of Docking Accuracy","volume":"47","author":"RA Friesner","year":"2004","journal-title":"J Med Chem [Internet]"},{"issue":"21","key":"pcbi.1010947.ref019","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes","volume":"49","author":"RA Friesner","year":"2006","journal-title":"J Med Chem [Internet]"},{"issue":"7","key":"pcbi.1010947.ref020","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1021\/jm030644s","article-title":"Glide: A New Approach for Rapid, Accurate Docking and Scoring. 2. Enrichment Factors in Database Screening","volume":"47","author":"TA Halgren","year":"2004","journal-title":"J Med Chem [Internet]"},{"issue":"7","key":"pcbi.1010947.ref021","doi-asserted-by":"crossref","first-page":"e0132508","DOI":"10.1371\/journal.pone.0132508","article-title":"Fully Flexible Docking of Medium Sized Ligand Libraries with RosettaLigand.","volume":"10","author":"S DeLuca","year":"2015","journal-title":"PLoS One [Internet]"},{"journal-title":"Protein\u2013Lipid Docking\u2014Profacgen [Internet]","year":"2022","key":"pcbi.1010947.ref022"},{"issue":"4","key":"pcbi.1010947.ref023","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.bbamem.2010.12.008","article-title":"Lipid-binding surfaces of membrane proteins: Evidence from evolutionary and structural analysis","volume":"1808","author":"L Adamian","year":"2011","journal-title":"Biochim Biophys Acta Biomembr"},{"issue":"9","key":"pcbi.1010947.ref024","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1016\/j.bpj.2021.02.028","article-title":"Structural determinants of cholesterol recognition in helical integral membrane proteins","volume":"120","author":"B Marlow","year":"2021","journal-title":"Biophys J [Internet]"},{"issue":"12","key":"pcbi.1010947.ref025","doi-asserted-by":"crossref","first-page":"e1000585","DOI":"10.1371\/journal.pcbi.1000585","article-title":"Predicting Protein Ligand Binding Sites by Combining Evolutionary Sequence Conservation and 3D Structure","volume":"5","author":"JA Capra","year":"2009","journal-title":"PLoS Comput Biol [Internet]"},{"issue":"9","key":"pcbi.1010947.ref026","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1004398","article-title":"An Integrated Framework Advancing Membrane Protein Modeling and Design","volume":"11","author":"RF Alford","year":"2015","journal-title":"PLoS Comput Biol"},{"issue":"8","key":"pcbi.1010947.ref027","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1016\/j.bpj.2020.03.006","article-title":"Protein Structure Prediction and Design in a Biologically Realistic Implicit Membrane","volume":"118","author":"RF Alford","year":"2020","journal-title":"Biophys J [Internet]"},{"key":"pcbi.1010947.ref028","article-title":"Assessing multiple score functions in Rosetta for drug discovery.","author":"ST Smith","year":"2020","journal-title":"PLoS One [Internet]"},{"issue":"7625","key":"pcbi.1010947.ref029","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nature19791","article-title":"Accurate de novo design of hyperstable constrained peptides","volume":"538","author":"G Bhardwaj","year":"2016","journal-title":"Nature [Internet]"},{"key":"pcbi.1010947.ref030","article-title":"OPM database and PPM web server: resources for positioning of proteins in membranes","volume":"40","author":"MA Lomize","year":"2012","journal-title":"Nucleic Acids Res [Internet]"},{"key":"pcbi.1010947.ref031","doi-asserted-by":"crossref","first-page":"021931","DOI":"10.1103\/PhysRevE.80.021931","article-title":"Effect of cholesterol on structural and mechanical properties of membranes depends on lipid chain saturation","volume":"80","author":"J Pan","year":"2009","journal-title":"Phys Rev E Stat Nonlin Soft Matter Phys [Internet]"},{"key":"pcbi.1010947.ref032","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.chemphyslip.2012.12.006","article-title":"How sterol tilt regulates properties and organization of lipid membranes and membrane insertions","volume":"169","author":"G Khelashvili","year":"2013","journal-title":"Chem Phys Lipids [Internet]"},{"issue":"22","key":"pcbi.1010947.ref033","doi-asserted-by":"crossref","first-page":"7524","DOI":"10.1021\/jp101889k","article-title":"Cholesterol orientation and tilt modulus in DMPC bilayers","volume":"114","author":"G Khelashvili","year":"2010","journal-title":"J Phys Chem B [Internet]"},{"issue":"27","key":"pcbi.1010947.ref034","doi-asserted-by":"crossref","first-page":"7090","DOI":"10.1021\/bi800123b","article-title":"Cholesterol is found to reside in the center of a polyunsaturated lipid membrane","volume":"47","author":"TA Harroun","year":"2008","journal-title":"Biochemistry [Internet]."},{"issue":"3","key":"pcbi.1010947.ref035","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1039\/b504527d","article-title":"How lipids and proteins interact in a membrane: a molecular approach","volume":"1","author":"AG Lee","year":"2005","journal-title":"Mol Biosyst [Internet]"},{"issue":"6","key":"pcbi.1010947.ref036","doi-asserted-by":"crossref","first-page":"4081","DOI":"10.1529\/biophysj.105.070755","article-title":"The interfacial lipid binding site on the potassium channel KcsA is specific for anionic phospholipids","volume":"89","author":"P Marius","year":"2005","journal-title":"Biophys J [Internet]"},{"issue":"15","key":"pcbi.1010947.ref037","doi-asserted-by":"crossref","first-page":"5873","DOI":"10.1021\/bi047439e","article-title":"Heterogeneity in the binding of lipid molecules to the surface of a membrane protein: hot spots for anionic lipids on the mechanosensitive channel of large conductance MscL and effects on conformation","volume":"44","author":"AM Powl","year":"2005","journal-title":"Biochemistry [Internet]."},{"issue":"2","key":"pcbi.1010947.ref038","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/0005-2736(82)90447-3","article-title":"Annular and non-annular binding sites on the (Ca2+ + Mg2+)-ATPase","volume":"693","author":"AC Simmonds","year":"1982","journal-title":"Biochim Biophys Acta [Internet]"},{"issue":"5","key":"pcbi.1010947.ref039","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1529\/biophysj.107.117507","article-title":"Binding of anionic lipids to at least three nonannular sites on the potassium channel KcsA is required for channel opening","volume":"94","author":"P Marius","year":"2008","journal-title":"Biophys J [Internet]."},{"issue":"10","key":"pcbi.1010947.ref040","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1016\/j.bpj.2014.10.011","article-title":"Two classes of cholesterol binding sites for the \u03b22AR revealed by thermostability and NMR","volume":"107","author":"DL Gater","year":"2014","journal-title":"Biophys J"},{"issue":"5854","key":"pcbi.1010947.ref041","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1126\/science.1150577","article-title":"High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor","volume":"318","author":"V Cherezov","year":"2007","journal-title":"Science [Internet]"},{"issue":"4","key":"pcbi.1010947.ref042","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1021\/jp3118192","article-title":"Mapping the functional binding sites of cholesterol in \u03b22- adrenergic receptor by long-time molecular dynamics simulations","volume":"117","author":"X Cang","year":"2013","journal-title":"Journal of Physical Chemistry B [Internet]"},{"issue":"5","key":"pcbi.1010947.ref043","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.str.2021.01.004","article-title":"Predictable cholesterol binding sites in GPCRs lack consensus motifs","volume":"29","author":"GJ Taghon","year":"2021","journal-title":"Structure"},{"issue":"6","key":"pcbi.1010947.ref044","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.str.2008.05.001","article-title":"A specific cholesterol binding site is established by the 2.8 \u00c5 structure of the human \u03b22-adrenergic receptor in an alternate crystal form","volume":"16","author":"MA Hanson","year":"2008","journal-title":"Structure [Internet]"},{"key":"pcbi.1010947.ref045","article-title":"Enantioselective protein-sterol interactions mediate regulation of both prokaryotic and eukaryotic inward rectifier K+ channels by cholesterol.","author":"N D\u2019Avanzo","year":"2011","journal-title":"PLoS One [Internet]"},{"issue":"6","key":"pcbi.1010947.ref046","doi-asserted-by":"crossref","first-page":"3211","DOI":"10.1016\/S0006-3495(02)75323-X","article-title":"Modulation of endothelial inward-rectifier K+ current by optical isomers of cholesterol","volume":"83","author":"VG Romanenko","year":"2002","journal-title":"Biophys J [Internet]"},{"key":"pcbi.1010947.ref047","unstructured":"Molecular Operating Environment (MOE) | MOEsaic | PSILO [Internet]. [cited 2022 Aug 10]. Available from: https:\/\/www.chemcomp.com\/Products.htm"},{"issue":"2","key":"pcbi.1010947.ref048","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/nrm2330","article-title":"Membrane lipids: where they are and how they behave","volume":"9","author":"G van Meer","year":"2008","journal-title":"Nat Rev Mol Cell Biol [Internet]"},{"journal-title":"The Boltzmann equation","author":"GE Lee","key":"pcbi.1010947.ref049"},{"issue":"2","key":"pcbi.1010947.ref050","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.jmb.2008.11.010","article-title":"RosettaLigand Docking with Full Ligand and Receptor Flexibility","volume":"385","author":"IW Davis","year":"2009","journal-title":"J Mol Biol"},{"key":"pcbi.1010947.ref051","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/978-1-61779-465-0_10","article-title":"Rosetta Ligand docking with flexible XML protocols","volume":"819","author":"G Lemmon","year":"2012","journal-title":"Methods Mol Biol [Internet]"},{"issue":"9","key":"pcbi.1010947.ref052","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1016\/j.bbamem.2015.03.012","article-title":"General and specific lipid\u2013protein interactions in Na,K-ATPase","volume":"1848","author":"F Cornelius","year":"2015","journal-title":"Biochimica et Biophysica Acta (BBA)\u2014Biomembranes"},{"issue":"11","key":"pcbi.1010947.ref053","doi-asserted-by":"crossref","first-page":"2904","DOI":"10.1073\/pnas.1620799114","article-title":"Specific phospholipid binding to Na,K-ATPase at two distinct sites","volume":"114","author":"M Habeck","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"15","key":"pcbi.1010947.ref054","doi-asserted-by":"crossref","first-page":"5956","DOI":"10.1074\/jbc.RA118.006223","article-title":"Cholesterol depletion inhibits Na+,K+-ATPase activity in a near-native membrane environment","volume":"294","author":"A Garcia","year":"2019","journal-title":"J Biol Chem [Internet]"},{"issue":"5","key":"pcbi.1010947.ref055","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1021\/acs.jpclett.5b00197","article-title":"Specific binding of cholesterol to the amyloid precursor protein: Structure of the complex and driving forces characterized in molecular detail","volume":"6","author":"\u0141 Nierzwicki","year":"2015","journal-title":"Journal of Physical Chemistry Letters [Internet]"},{"issue":"7","key":"pcbi.1010947.ref056","doi-asserted-by":"crossref","first-page":"935","DOI":"10.3390\/biom11070935","article-title":"The role of cholesterol in amyloidogenic substrate binding to the \u03b3-secretase complex.","volume":"11","author":"U Orze\u0142","year":"2021","journal-title":"Biomolecules [Internet]"},{"issue":"1","key":"pcbi.1010947.ref057","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1006\/nbdi.2001.0470","article-title":"Cholesterol-dependent \u03b3-secretase activity in buoyant cholesterol-rich membrane microdomains","volume":"9","author":"S Wahrle","year":"2002","journal-title":"Neurobiol Dis [Internet]"},{"issue":"1","key":"pcbi.1010947.ref058","first-page":"1","article-title":"Palmitoylation and membrane cholesterol stabilize \u03bc-opioid receptor homodimerization and G protein coupling","volume":"13","author":"H Zheng","year":"2012","journal-title":"BMC Cell Biol [Internet]"},{"issue":"33","key":"pcbi.1010947.ref059","doi-asserted-by":"crossref","first-page":"22108","DOI":"10.1074\/jbc.M109.030411","article-title":"Differential Effect of Membrane Cholesterol Removal on \u03bc- and \u03b4-Opioid Receptors: A PARALLEL COMPARISON OF ACUTE AND CHRONIC SIGNALING TO ADENYLYL CYCLASE*","volume":"284","author":"ES Levitt","year":"2009","journal-title":"J Biol Chem [Internet]"},{"issue":"8","key":"pcbi.1010947.ref060","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1016\/j.jmb.2019.02.030","article-title":"Influence of Cholesterol and Its Stereoisomers on Members of the Serotonin Receptor Family","volume":"431","author":"V Oakes","year":"2019","journal-title":"J Mol Biol [Internet]"},{"issue":"6085","key":"pcbi.1010947.ref061","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1126\/science.1219988","article-title":"The Amyloid Precursor Protein has a Flexible Transmembrane Domain and Binds Cholesterol","volume":"336","author":"PJ Barrett","year":"2012","journal-title":"Science [Internet]"},{"issue":"6","key":"pcbi.1010947.ref062","doi-asserted-by":"crossref","first-page":"e20161","DOI":"10.1371\/journal.pone.0020161","article-title":"RosettaScripts: A Scripting Language Interface to the Rosetta Macromolecular Modeling Suite.","volume":"6","author":"SJ Fleishman","year":"2011","journal-title":"PLoS One [Internet]"},{"issue":"2","key":"pcbi.1010947.ref063","article-title":"ConSurf 2010: Calculating evolutionary conservation in sequence and structure of proteins and nucleic acids","volume":"38","author":"H Ashkenazy","year":"2010","journal-title":"Nucleic Acids Res"},{"issue":"W1","key":"pcbi.1010947.ref064","doi-asserted-by":"crossref","first-page":"W344","DOI":"10.1093\/nar\/gkw408","article-title":"ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules","volume":"44","author":"H Ashkenazy","year":"2016","journal-title":"Nucleic Acids Res [Internet]"},{"issue":"2","key":"pcbi.1010947.ref065","article-title":"ConSurf 2005: The projection of evolutionary conservation scores of residues on protein structures","volume":"33","author":"M Landau","year":"2005","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pcbi.1010947.ref066","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/bioinformatics\/19.1.163","article-title":"ConSurf: Identification of functional regions in proteins by surface-mapping of phylogenetic information","volume":"19","author":"F Glaser","year":"2003","journal-title":"Bioinformatics"},{"volume-title":"Bioinformatics.","year":"2002","author":"T Pupko","key":"pcbi.1010947.ref067"},{"issue":"6","key":"pcbi.1010947.ref068","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1093\/bioinformatics\/btu739","article-title":"UniRef clusters: a comprehensive and scalable alternative for improving sequence similarity searches","volume":"31","author":"BE Suzek","year":"2015","journal-title":"Bioinformatics [Internet]."},{"issue":"W1","key":"pcbi.1010947.ref069","doi-asserted-by":"crossref","first-page":"W510","DOI":"10.1093\/nar\/gkac439","article-title":"NetSurfP-3.0: accurate and fast prediction of protein structural features by protein language models and deep learning","volume":"50","author":"MH H\u00f8ie","year":"2022","journal-title":"Nucleic Acids Res [Internet]"},{"issue":"6","key":"pcbi.1010947.ref070","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1002\/prot.25674","article-title":"NetSurfP-2.0: Improved prediction of protein structural features by integrated deep learning","volume":"87","author":"MS Klausen","year":"2019","journal-title":"Proteins: Structure, Function and Bioinformatics"},{"issue":"1","key":"pcbi.1010947.ref071","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s12859-017-1541-z","article-title":"Computing structure-based lipid accessibility of membrane proteins with mp_lipid_acc in RosettaMP","volume":"18","author":"J Koehler Leman","year":"2017","journal-title":"BMC Bioinformatics"},{"issue":"10","key":"pcbi.1010947.ref072","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1002\/jcc.21787","article-title":"MDAnalysis: A toolkit for the analysis of molecular dynamics simulations","volume":"32","author":"N Michaud-Agrawal","year":"2011","journal-title":"J Comput Chem [Internet]"},{"key":"pcbi.1010947.ref073","doi-asserted-by":"crossref","DOI":"10.25080\/Majora-629e541a-00e","article-title":"MDAnalysis: A Python Package for the Rapid Analysis of Molecular Dynamics Simulations","author":"RJ Gowers","year":"2016","journal-title":"PROC OF THE 15th PYTHON IN SCIENCE CONF [Internet]"},{"issue":"406","key":"pcbi.1010947.ref074","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1080\/01621459.1989.10478785","article-title":"Advances in record-linkage methodology as applied to matching the 1985 census of Tampa, Florida","volume":"84","author":"MA Jaro","year":"1989","journal-title":"J Am Stat Assoc"},{"journal-title":"String Comparator Metrics and Enhanced Decision Rules in the Fellegi-Sunter Model of Record Linkage","year":"1990","author":"WE Winkler","key":"pcbi.1010947.ref075"},{"issue":"1","key":"pcbi.1010947.ref076","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/prot.22315","article-title":"A Unified Hydrophobicity Scale for Multi-Span Membrane Proteins","volume":"76","author":"J Koehler","year":"2009","journal-title":"Proteins [Internet]"},{"key":"pcbi.1010947.ref077","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0079-6107(72)90005-3","article-title":"Protein volume in solution","volume":"24","author":"AA Zamyatnin","year":"1972","journal-title":"Prog Biophys Mol Biol"},{"issue":"18","key":"pcbi.1010947.ref078","doi-asserted-by":"crossref","first-page":"3499","DOI":"10.1093\/bioinformatics\/btz062","article-title":"Calculation of accurate interatomic contact surface areas for the quantitative analysis of non-bonded molecular interactions","volume":"35","author":"J Ribeiro","year":"2019","journal-title":"Bioinformatics [Internet]"},{"issue":"9","key":"pcbi.1010947.ref079","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.bpj.2019.03.025","article-title":"Interfacial Binding Sites for Cholesterol on G Protein-Coupled Receptors","volume":"116","author":"AG Lee","year":"2019","journal-title":"Biophys J [Internet]"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1010947","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T17:23:33Z","timestamp":1679937813000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1010947"}},"subtitle":[],"editor":[{"given":"Nir","family":"Ben-Tal","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2023,3,27]]},"references-count":79,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1010947","relation":{},"ISSN":["1553-7358"],"issn-type":[{"type":"electronic","value":"1553-7358"}],"subject":[],"published":{"date-parts":[[2023,3,27]]}}}