{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T22:11:25Z","timestamp":1778623885448,"version":"3.51.4"},"reference-count":55,"publisher":"The Royal Society","issue":"2080","license":[{"start":{"date-parts":[[2016,11,13]],"date-time":"2016-11-13T00:00:00Z","timestamp":1478995200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"name":"amfAR Mathilde Krim Fellowship","award":["108680"],"award-info":[{"award-number":["108680"]}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Phil. Trans. R. Soc. A."],"published-print":{"date-parts":[[2016,11,13]]},"abstract":"<jats:p>\n                    Retrovirus particle (virion) infectivity requires diffusion and clustering of multiple transmembrane envelope proteins (Env\n                    <jats:sub>3<\/jats:sub>\n                    ) on the virion exterior, yet is triggered by protease-dependent degradation of a partially occluding, membrane-bound Gag polyprotein lattice on the virion interior. The physical mechanism underlying such coupling is unclear and only indirectly accessible via experiment. Modelling stands to provide insight but the required spatio-temporal range far exceeds current accessibility by all-atom or even coarse-grained molecular dynamics simulations. Nor do such approaches account for chemical reactions, while conversely, reaction kinetics approaches handle neither diffusion nor clustering. Here, a recently developed multiscale approach is considered that applies an ultra-coarse-graining scheme to treat entire proteins at near-single particle resolution, but which also couples chemical reactions with diffusion and interactions. A model is developed of Env\n                    <jats:sub>3<\/jats:sub>\n                    molecules embedded in a truncated Gag lattice composed of membrane-bound matrix proteins linked to capsid subunits, with freely diffusing protease molecules. Simulations suggest that in the presence of Gag but in the absence of lateral lattice-forming interactions, Env\n                    <jats:sub>3<\/jats:sub>\n                    diffuses comparably to Gag-absent Env\n                    <jats:sub>3<\/jats:sub>\n                    . Initial immobility of Env\n                    <jats:sub>3<\/jats:sub>\n                    is conferred through lateral caging by matrix trimers vertically coupled to the underlying hexameric capsid layer. Gag cleavage by protease vertically decouples the matrix and capsid layers, induces both matrix and Env\n                    <jats:sub>3<\/jats:sub>\n                    diffusion, and permits Env\n                    <jats:sub>3<\/jats:sub>\n                    clustering. Spreading across the entire membrane surface reduces crowding, in turn, enhancing the effect and promoting infectivity.\n                  <\/jats:p>\n                  <jats:p>This article is part of the themed issue \u2018Multiscale modelling at the physics\u2013chemistry\u2013biology interface\u2019.<\/jats:p>","DOI":"10.1098\/rsta.2016.0148","type":"journal-article","created":{"date-parts":[[2016,10,3]],"date-time":"2016-10-03T21:00:41Z","timestamp":1475528441000},"page":"20160148","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Reaction\u2013diffusion basis of retroviral infectivity"],"prefix":"10.1098","volume":"374","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5112-0307","authenticated-orcid":false,"given":"S. Kashif","family":"Sadiq","sequence":"first","affiliation":[{"name":"Infection Biology Unit, Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB), C\/Doctor Aiguader 88, 08003 Barcelona, Spain"},{"name":"Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), Schloss-Wolfsbrunnenweg 35, 69118 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","published-online":{"date-parts":[[2016,11,13]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006924"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00242"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601664"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903535106"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13838"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.7.3099"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2009.02.048"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2008.10.013"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.16.8477-8485.2004"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.17.7970"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02997-14"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5398.80"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2005.09.010"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12162"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000669"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-440X(99)80033-5"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1998.9398"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6854"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2012.10.006"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb785"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01408-13"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg143"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/35030177"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3490"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.04.042"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2015.09.003"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004595"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.2.1026-1031.2004"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1226359"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2009.09.049"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2012.09.007"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11568"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevE.74.031912"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevLett.102.198102"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2015.08.017"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevLett.96.078102"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevE.72.051923"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp206321b"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003103"},{"key":"e_1_3_4_41_2","first-page":"1","article-title":"Modeling viral capsid assembly","volume":"155","author":"Hagan MF","year":"2014","journal-title":"Adv. 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