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
References
Oct 1, 1975·Biophysical Chemistry·B Goldstein
Dec 1, 1992·Scientific American·G F Joyce
Jul 1, 1992·Trends in Biochemical Sciences·J K Scott
Jul 27, 1990·Science·J K Scott, G P Smith
Aug 30, 1990·Nature·A D Ellington, J W Szostak
Aug 3, 1990·Science·C Tuerk, L Gold
Nov 10, 1988·Journal of Immunological Methods·H Nygren
Dec 1, 1989·Journal of Molecular Evolution·C AmitranoM Saber
Dec 20, 1988·Gene·S F Parmley, G P Smith
Feb 7, 1970·Nature·J M Smith
Jan 1, 1994·Molecular Biology Reports·S J Klug, M Famulok
Apr 1, 1995·Biophysical Journal·B Goldstein, M Dembo
Jan 1, 1994·Annual Review of Immunology·G WinterH R Hoogenboom
Jun 15, 1994·European Journal of Biochemistry·V Gailus, I Rasched
Sep 1, 1993·Molecular Immunology·J E ButlerE W Voss
Apr 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·D LancetE Seidemann
Jul 15, 1996·Mathematical Biosciences·B Sulzer, A S Perelson
Sep 1, 1995·Molecular Diversity·B Levitan, S Kauffman
Citations
Oct 26, 2010·Nature Biotechnology·Hongyuan MaoVaughn V Smider
Nov 26, 1999·Immunology and Cell Biology·J M DaviesI R MacKay
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
May 23, 2006·Infection and Immunity·Rasmus LundquistMorten Hanefeld Dziegiel
Jan 15, 2014·Computational and Mathematical Methods in Medicine·Wadim L Matochko, Ratmir Derda
Nov 5, 2015·Bioconjugate Chemistry·Erik D WoldVaughn V Smider
Apr 18, 2015·PLoS Computational Biology·Xiliang Zheng, Jin Wang
Jan 4, 2005·Journal of Immunological Methods·David L JayeCharles A Parkos
Feb 3, 2004·Journal of Receptor and Signal Transduction Research·Michael Szardenings
Apr 23, 2008·Current Protocols in Nucleic Acid Chemistry·B Vant-HullD A Zichi
May 8, 2002·The Journal of Biological Chemistry·Kevin G HoffLarry E Vickery
Feb 23, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ratmir DerdaMohammad R Jafari
Dec 15, 2007·Nature Protocols·Steffen U EisenhardtKarlheinz Peter
Apr 8, 2009·Lab on a Chip·Yanli LiuH Tom Soh
May 24, 2012·Biotechnology & Genetic Engineering Reviews·Hongyuan MaoVaughn V Smider
Aug 9, 2017·Genome Biology·Alan F RubinDouglas M Fowler
Dec 31, 2000·The Journal of Biological Chemistry·G PetersenU Gehring
Jan 30, 2004·Cancer Immunology, Immunotherapy : CII·Alexander FossåErlend B Smeland
Feb 13, 2001·European Journal of Biochemistry·T L ErikssonM van Hage-Hamsten
Sep 4, 2008·Biotechnology and Bioengineering·Susan B CurtisW Scott Dunbar
Aug 5, 2017·Antibodies·Mohamed A AlfalehStephen M Mahler
Oct 8, 1999·Biochemistry·M D FinucaneD N Woolfson
Oct 18, 2000·Journal of Immunological Methods·F HammondR Ward
Mar 5, 2013·Immunology Letters·Meina Neumann-SchaalKatja Heilmann
Nov 17, 2001·Chemical Reviews·R H Hoess
May 14, 2003·Biochemistry·Bernadette HeydPhilippe Minard
Apr 21, 2009·Biotechnology Advances·Nina E Weisser, J Christopher Hall
Dec 17, 2010·Journal of Chromatography. a·Jane T MooneyMilton T W Hearn