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Phys."},{"key":"10.1016\/j.bpj.2025.04.020_bib82","doi-asserted-by":"crossref","DOI":"10.1088\/0953-8984\/21\/46\/463102","article-title":"Forward flux sampling for rare event simulations","volume":"21","author":"Allen","year":"2009","journal-title":"J. Phys. Condens. Matter"},{"key":"10.1016\/j.bpj.2025.04.020_bib83","series-title":"Understanding Molecular Simulation: From Algorithms to Applications","author":"Frenkel","year":"2023"},{"key":"10.1016\/j.bpj.2025.04.020_bib84","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0006-3495(96)79552-8","article-title":"Weighted-ensemble Brownian dynamics simulations for protein association reactions","volume":"70","author":"Huber","year":"1996","journal-title":"Biophys. J."},{"key":"10.1016\/j.bpj.2025.04.020_bib85","doi-asserted-by":"crossref","DOI":"10.1063\/1.3518708","article-title":"A multiple replica approach to simulate reactive trajectories","volume":"134","author":"C\u00e9rou","year":"2011","journal-title":"J. Chem. 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