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TitleFacilitated diffusion models for gene regulation in living cells
LanguageEnglish
File Size3.8 MB
Total Pages131
Table of Contents
                            Introduction
	Historical notes: from Plato to Watson and Crick
		Mendel's experiments
		Twentieth centrury: Mendel reloaded
		Hereditary information: in proteins or in DNA?
	The central dogma of molecular biology
		The structure of DNA
		RNA and transcription
		Proteins and translation
		Scheme of the central dogma
	Gene regulation in prokaryotes
		E. coli and its metabolism
		Lac operon and its control
	There is more than just O1
		The symmetric operator Osym
		The auxiliary operators
		Structure of the lac repressor
		Looping
		Connection to information theory
	Sequence specificity and non-specific binding
		Thermodynamic models
Biological search processes
	The diffusion limit
		First passage time formalism
		Experimental results by Riggs et al.
		Extension of Smoluchowski's formula
	Early studies
		Reduction of dimensionality
		The contributions of Peter H. Richter
		The contributions of Otto G. Berg
	The Berg-von Hippel or facilitated diffusion model
		How is sliding made possible biologically?
	Modern studies
		Experimental studies
		Theoretical studies
		Computational models
		Two-state models and the speed-stability paradox
	General features of the model and criticism
		General features
		Modern criticism
Generalised facilitated diffusion model
	The model
		3D kernel functions for the straight DNA conformation
		Solution of the differential equations
	Results of GFDM for straight DNA
		Result obtained with the reference parameter values
		Dependence on the switching rates krs and ksr
		Dependence on the diffusion coefficients
		Dependence on the reaction volume
	Results for coiled DNA
	Relation to previously published models
	Summary and outlook
In vivo facilitated diffusion model
	Organisation of bacterial DNA
		Model genome
	General search model
		Details of the search model
	Microscopic model
		Derivation of the target detection probability, pt
		Derivation of the non-specific association probability, pr
	Derivation of the mean target search time
	Results of the IVFDM
		Reference set of parameters
		Bound fraction of time
		Mean search time
		Searching at near optimal conditions
		Influence of different parameter sets
		Acceleration due to local searches
	Summary and outlook
Target search in a real sequence
	Search in the target region
		Score matrix
		Relation between scores and energies
		Reference set of parameters
		Theoretical model
	Results for the search in the target region
		Probability to detect the target
		Impedance matching
		Conditional target detection time
		Probability of first detecting O1
	Full search model
	Results for the full search model
		Dependence on a
		Looping effects
		Blocker conformation effects
	Summary
Discussion and outlook
                        

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