scholarly journals A Systems Approach to Measuring the Binding Energy Landscapes of Transcription Factors

Science ◽  
2007 ◽  
Vol 315 (5809) ◽  
pp. 233-237 ◽  
Author(s):  
Sebastian J. Maerkl ◽  
Stephen R. Quake
Keyword(s):  
Transcription Factors ◽  
Binding Energy ◽  
High Throughput ◽  
Molecular Interactions ◽  
Biological Networks ◽  
Systems Approach ◽  
Energy Landscapes ◽  
Eukaryotic Transcription ◽  
Network Topologies

A major goal of systems biology is to predict the function of biological networks. Although network topologies have been successfully determined in many cases, the quantitative parameters governing these networks generally have not. Measuring affinities of molecular interactions in high-throughput format remains problematic, especially for transient and low-affinity interactions. We describe a high-throughput microfluidic platform that measures such properties on the basis of mechanical trapping of molecular interactions. With this platform we characterized DNA binding energy landscapes for four eukaryotic transcription factors; these landscapes were used to test basic assumptions about transcription factor binding and to predict their in vivo function.

Describing Delicate Interactions

2007 ◽  
Vol 2007 (369) ◽  
pp. tw24-tw24
Author(s):  
Valda Vinson
Keyword(s):  
Transcription Factors ◽  
Binding Energy ◽  
Dna Binding ◽  
High Throughput ◽  
Biological Networks ◽  
Full Text ◽  
Systems Approach ◽  
Energy Landscapes ◽  
Eukaryotic Transcription ◽  
Link Type

Quantifying the affinities of interactions in biological networks, particularly transient ones, remains a challenge. Maerkl and Quake describe a high-throughput microfluidic platform that allows the measurement of transient and low-affinity interactions and characterize the DNA binding energy landscapes for four eukaryotic transcription factors. In two cases, the binding specificities were used to predict which genes the transcription factors would bind and likely regulate.S. J. Maerkl, S. R. Quake, A systems approach to measuring the binding energy landscapes of transcription factors. Science315, 233-237 (2007). [Abstract][Full Text]

scholarly journals Controlling Supramolecular Plasticity through Stoichiometry

2019 ◽  
Author(s):  
David Komaromy ◽  
Theodora Tiemersma-Wegman ◽  
Johan Kemmink ◽  
Giuseppe Portale ◽  
Friso Aalbers ◽  
...  
Keyword(s):  
Binding Energy ◽  
Building Block ◽  
Systems Approach ◽  
Building Blocks ◽  
Supramolecular Assemblies ◽  
Energy Landscapes ◽  
Complex Energy ◽  
Thermodynamic Control ◽  
One To One

In this manuscript we describe how, by taking a systems approach, complex energy landscapes of supramolecular assemblies can be navigated using stoichiometry to control, with remarkable selectivity, which assembly gets populated. The perhaps counterintuitive finding is that it is not necessarily the assembly that, in a one-to-one comparison, is the most stable that wins the competition for common building blocks, even though the system is under thermodynamic control. Instead, an individually less stable assembly may completely dominate the system. This domination is possible when the building block stoichiometry in the system matches the stoichiometry of this specific assembly, allowing the system to maximize binding energy by making a large number of assemblies of moderate stability as opposed to a small number of more stable assemblies. <br>

scholarly journals Controlling Supramolecular Plasticity through Stoichiometry

2019 ◽  
Author(s):  
David Komaromy ◽  
Theodora Tiemersma-Wegman ◽  
Johan Kemmink ◽  
Giuseppe Portale ◽  
Friso Aalbers ◽  
...  
Keyword(s):  
Binding Energy ◽  
Building Block ◽  
Systems Approach ◽  
Building Blocks ◽  
Supramolecular Assemblies ◽  
Energy Landscapes ◽  
Complex Energy ◽  
Thermodynamic Control ◽  
One To One

In this manuscript we describe how, by taking a systems approach, complex energy landscapes of supramolecular assemblies can be navigated using stoichiometry to control, with remarkable selectivity, which assembly gets populated. The perhaps counterintuitive finding is that it is not necessarily the assembly that, in a one-to-one comparison, is the most stable that wins the competition for common building blocks, even though the system is under thermodynamic control. Instead, an individually less stable assembly may completely dominate the system. This domination is possible when the building block stoichiometry in the system matches the stoichiometry of this specific assembly, allowing the system to maximize binding energy by making a large number of assemblies of moderate stability as opposed to a small number of more stable assemblies. <br>

High resolution protein-DNA binding energy landscapes via a novel high throughput method

Biopolymers ◽  
2007 ◽  
Vol 85 (5-6) ◽  
pp. vii-viii ◽  
Author(s):  
G. Eric Plum ◽  
David N. Breslauer ◽  
Kenneth J. Breslauer
Keyword(s):  
High Resolution ◽  
Binding Energy ◽  
Dna Binding ◽  
High Throughput ◽  
Energy Landscapes ◽  
High Throughput Method

Subnuclear compartmentalization of sequence-specific transcription factors and regulation of eukaryotic gene expression

2005 ◽  
Vol 83 (4) ◽  
pp. 535-547 ◽  
Author(s):  
Gareth N Corry ◽  
D Alan Underhill
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Current Knowledge ◽  
Nuclear Architecture ◽  
Subnuclear Localization ◽  
Modular Structures

To date, the majority of the research regarding eukaryotic transcription factors has focused on characterizing their function primarily through in vitro methods. These studies have revealed that transcription factors are essentially modular structures, containing separate regions that participate in such activities as DNA binding, protein–protein interaction, and transcriptional activation or repression. To fully comprehend the behavior of a given transcription factor, however, these domains must be analyzed in the context of the entire protein, and in certain cases the context of a multiprotein complex. Furthermore, it must be appreciated that transcription factors function in the nucleus, where they must contend with a variety of factors, including the nuclear architecture, chromatin domains, chromosome territories, and cell-cycle-associated processes. Recent examinations of transcription factors in the nucleus have clarified the behavior of these proteins in vivo and have increased our understanding of how gene expression is regulated in eukaryotes. Here, we review the current knowledge regarding sequence-specific transcription factor compartmentalization within the nucleus and discuss its impact on the regulation of such processes as activation or repression of gene expression and interaction with coregulatory factors.Key words: transcription, subnuclear localization, chromatin, gene expression, nuclear architecture.

scholarly journals High-throughput screening and rational design of biofunctionalized surfaces with optimized biocompatibility and antimicrobial activity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhou Fang ◽  
Junjian Chen ◽  
Ye Zhu ◽  
Guansong Hu ◽  
Haoqian Xin ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
High Throughput ◽  
High Throughput Screening ◽  
Rational Design ◽  
Click Reaction ◽  
Reaction Times ◽  
Great Promise ◽  
Biomaterial Surfaces

AbstractPeptides are widely used for surface modification to develop improved implants, such as cell adhesion RGD peptide and antimicrobial peptide (AMP). However, it is a daunting challenge to identify an optimized condition with the two peptides showing their intended activities and the parameters for reaching such a condition. Herein, we develop a high-throughput strategy, preparing titanium (Ti) surfaces with a gradient in peptide density by click reaction as a platform, to screen the positions with desired functions. Such positions are corresponding to optimized molecular parameters (peptide densities/ratios) and associated preparation parameters (reaction times/reactant concentrations). These parameters are then extracted to prepare nongradient mono- and dual-peptide functionalized Ti surfaces with desired biocompatibility or/and antimicrobial activity in vitro and in vivo. We also demonstrate this strategy could be extended to other materials. Here, we show that the high-throughput versatile strategy holds great promise for rational design and preparation of functional biomaterial surfaces.

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