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The strength and specificity of proteins binding to a membrane depend on the lipid composition. Single-particle reaction-diffusion methods offer a powerful tool for capturing lipid-specific binding to membrane surfaces by treating lipids explicitly as individual diffusible binding sites. However, modeling lipid particle populations is expensive. Here, we present an algorithm for reversible binding of proteins to continuum surfaces with implicit lipids, providing dramatic speed-ups to many body simulations. Our algorithm can be readily integrated into most reaction-diffusion software packages. We characterize changes to kinetics that emerge from explicit vs implicit lipids as well as surface adsorption models, showing excellent agreement between our method and the full explicit lipid model. Compared to models of surface adsorption, which couple together binding affinity and lipid concentration, our implicit lipid model decouples them to provide more flexibility for controlling surface binding properties and lipid inhomogeneity, thus reproducing binding kinetics and equilibria. Crucially, we demonstrate our method\u2019s application to membranes of arbitrary curvature and topology, modeled via a subdivision limit surface, again showing excellent agreement with explicit lipid simulations. Unlike adsorption models, our method retains the ability to bind lipids after proteins are localized to the surface (through, e.g., a protein-protein interaction), which can greatly increase the stability of multiprotein complexes on the surface. Our method will enable efficient cell-scale simulations involving proteins localizing to realistic membrane models, which is a critical step for predictive modeling and quantification of in vitro and in vivo dynamics.<\/jats:p>","DOI":"10.1063\/1.5120516","type":"journal-article","created":{"date-parts":[[2019,9,30]],"date-time":"2019-09-30T18:39:33Z","timestamp":1569868773000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["An implicit lipid model for efficient reaction-diffusion simulations of protein binding to surfaces of arbitrary topology"],"prefix":"10.1063","volume":"151","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6043-5183","authenticated-orcid":false,"given":"Yiben","family":"Fu","sequence":"first","affiliation":[{"name":"T. C. Jenkins Department of Biophysics, Johns Hopkins University 1 , 3400 N. Charles St., Baltimore, Maryland 21218, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osman N.","family":"Yogurtcu","sequence":"additional","affiliation":[{"name":"T. C. Jenkins Department of Biophysics, Johns Hopkins University 1 , 3400 N. 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