How the DNA sequence affects the Hill curve of transcriptional response

The Hill coefficient is often used as a direct measure of the cooperativity of binding processes. It is an essential tool for probing properties of reactions in many biochemical systems. Here we analyze existing experimental data and demonstrate that the Hill coefficient characterizing the binding of transcription factors to their cognate sites can in fact be larger than one -- the standard indication of cooperativity -- even in the absence of any standard cooperative binding mechanism. By studying the problem analytically, we demonstrate that this effect occurs due to the disordered binding energy of the transcription factor to the DNA molecule and the steric interactions between the different copies of the transcription factor. We show that the enhanced Hill coefficient implies a significant reduction in the number of copies of the transcription factors which is needed to occupy a cognate site and, in many cases, can explain existing estimates for numbers of the transcription factors in cells. The mechanism is general and should be applicable to other biological recognition processes.Comment: 9 pages, 7 figure

Classes of fast and specific search mechanisms for proteins on DNA

Problems of search and recognition appear over different scales in biological systems. In this review we focus on the challenges posed by interactions between proteins, in particular transcription factors, and DNA and possible mechanisms which allow for a fast and selective target location. Initially we argue that DNA-binding proteins can be classified, broadly, into three distinct classes which we illustrate using experimental data. Each class calls for a different search process and we discuss the possible application of different search mechanisms proposed over the years to each class. The main thrust of this review is a new mechanism which is based on barrier discrimination. We introduce the model and analyze in detail its consequences. It is shown that this mechanism applies to all classes of transcription factors and can lead to a fast and specific search. Moreover, it is shown that the mechanism has interesting transient features which allow for stability at the target despite rapid binding and unbinding of the transcription factor from the target.Comment: 65 pages, 23 figure

Classical R-Matrices and the Feigin-Odesskii Algebra via Hamiltonian and Poisson Reductions

We present a formula for a classical $r$-matrix of an integrable system obtained by Hamiltonian reduction of some free field theories using pure gauge symmetries. The framework of the reduction is restricted only by the assumption that the respective gauge transformations are Lie group ones. Our formula is in terms of Dirac brackets, and some new observations on these brackets are made. We apply our method to derive a classical $r$-matrix for the elliptic Calogero-Moser system with spin starting from the Higgs bundle over an elliptic curve with marked points. In the paper we also derive a classical Feigin-Odesskii algebra by a Poisson reduction of some modification of the Higgs bundle over an elliptic curve. This allows us to include integrable lattice models in a Hitchin type construction.Comment: 27 pages LaTe

Effects of intersegmental transfers on target location by proteins

We study a model for a protein searching for a target, using facilitated diffusion, on a DNA molecule confined in a finite volume. The model includes three distinct pathways for facilitated diffusion: (a) sliding - in which the protein diffuses along the contour of the DNA (b) jumping - where the protein travels between two sites along the DNA by three-dimensional diffusion, and finally (c) intersegmental transfer - which allows the protein to move from one site to another by transiently binding both at the same time. The typical search time is calculated using scaling arguments which are verified numerically. Our results suggest that the inclusion of intersegmental transfer (i) decreases the search time considerably (ii) makes the search time much more robust to variations in the parameters of the model and (iii) that the optimal search time occurs in a regime very different than that found for models which ignore intersegmental transfers. The behavior we find is rich and shows surprising dependencies, for example, on the DNA length.Comment: 40 pages, 14 figure

Search reliability and search efficiency of combined Lévy–Brownian motion: long relocations mingled with thorough local exploration

A combined dynamics consisting of Brownian motion and Levy flights is exhibited by a variety of biological systems performing search processes. Assessing the search reliability of ever locating the target and the search efficiency of doing so economically of such dynamics thus poses an important problem. Here we model this dynamics by a one-dimensional fractional Fokker-Planck equation combining unbiased Brownian motion and Levy flights. By solving this equation both analytically and numerically we show that the superposition of recurrent Brownian motion and Levy flights with stable exponent α<1, by itself implying zero probability of hitting a point on a line, lead to transient motion with finite probability of hitting any point on the line. We present results for the exact dependence of the values of both the search reliability and the search efficiency on the distance between the starting and target positions as well as the choice of the scaling exponent α of the Levy flight component

An analytic expression for the HBT extrinsic base-collector capacitance derived from S-parameter measurements

Direct extraction is the most accurate method for the determination of equivalent-circuits of heterojunction bipolar transistors (HBTs). However, previous work lacks an exact expression for the extrinsic base-collector capacitance, which models the distributed nature of the base. This paper gives the derivation of an exact expression for this capacitance. As a result, each intrinsic equivalent-circuit parameter is determined using a simple exact expression at each measured frequency. The expression is valid for both the hybrid- /spl pi/ and the physics-based T-topology equivalent circuits. Extraction results for InP- and GaAs-HBTs are given