Stochastic modeling and optimization of phage display

Journal of Molecular Biology
B Levitan

Abstract

Phage display, SELEX and other methods of combinatorial chemistry have become very popular means of finding ligands with high affinities to given targets. Despite their success, they suffer from numerous sources of error and bias, such as very low initial concentrations of species, non-specific binding, and the sampling of only a tiny fraction of the library at the end of an experiment. To understand the interaction of these errors and to better devise molecular search strategies that take the errors into account, I devise and analyze a highly detailed model of phage display. The model is specifically designed to study the influence of the stochastic nature of each laboratory step. The model includes phage multivalency, multiple classes of targets, and solid-phase equilibrium and washing, yet it is amenable to analytic results and rapid computer simulation. With both analytic and simulation approaches, I: (1) describe the effects of target concentration, phage valency, degree of background binding and other laboratory parameters on the probabilities of phage binding and of being selected; (2) show the effects of an increasing selection stringency strategy and how it results in a tradeoff between rapid library enrichment and hig...Continue Reading

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Citations

Apr 14, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jinpeng WangH Tom Soh
Jun 29, 2002·Applied and Environmental Microbiology·Sharon L Bishop-HurleyJames T English
Jan 15, 2014·Computational and Mathematical Methods in Medicine·Wadim L Matochko, Ratmir Derda
Nov 5, 2015·Bioconjugate Chemistry·Erik D WoldVaughn V Smider
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Feb 23, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ratmir DerdaMohammad R Jafari
May 24, 2012·Biotechnology & Genetic Engineering Reviews·Hongyuan MaoVaughn V Smider
Aug 9, 2017·Genome Biology·Alan F RubinDouglas M Fowler
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Jan 30, 2004·Cancer Immunology, Immunotherapy : CII·Alexander FossåErlend B Smeland
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Apr 21, 2009·Biotechnology Advances·Nina E Weisser, J Christopher Hall

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