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In gene expression, various kinds of proteins need to bind to specific locus of DNA. It is still not clear how these proteins find their target locus. In this study, the mean first-passage time (FPT) of protein binding to its target locus…

Biological Physics · Physics 2016-06-20 Jingwei Li , Yunxin Zhang

We present the first proof-of-concept simulations of detectors using biomaterials to detect particle interactions. The essential idea behind a "DNA detector" involves the attachment of a forest of precisely-sequenced single or…

In bacteria, regulatory proteins search for a specific DNA binding target via "facilitated diffusion": a series of rounds of 3D diffusion in the cytoplasm, and 1D linear diffusion along the DNA contour. Using large scale Brownian dynamics…

Biological Physics · Physics 2013-09-05 C. A. Brackley , M. E. Cates , D. Marenduzzo

Generating molecules that bind to specific proteins is an important but challenging task in drug discovery. Previous works usually generate atoms in an auto-regressive way, where element types and 3D coordinates of atoms are generated one…

Biomolecules · Quantitative Biology 2024-07-16 Haitao Lin , Yufei Huang , Odin Zhang , Siqi Ma , Meng Liu , Xuanjing Li , Lirong Wu , Jishui Wang , Tingjun Hou , Stan Z. Li

Proteins are known to locate their specific targets on DNA up to two orders of magnitude faster than predicted by the Smoluchowski three-dimensional diffusion rate. One of the mechanisms proposed to resolve this discrepancy is termed…

Biomolecules · Quantitative Biology 2011-11-10 Tao Hu , B. I. Shklovskii

Transcription factor (TF) molecules translocate by facilitated diffusion (a combination of 3D diffusion around and 1D random walk on the DNA). Despite the attention this mechanism received in the last 40 years, only a few studies…

Subcellular Processes · Quantitative Biology 2013-09-20 Nicolae Radu Zabet , Boris Adryan

Recent experiments show that transcription factors (TFs) indeed use the facilitated diffusion mechanism to locate their target sequences on DNA in living bacteria cells: TFs alternate between sliding motion along DNA and relocation events…

Quantitative Methods · Quantitative Biology 2015-07-10 Maximilian Bauer , Emil S. Rasmussen , Michael A. Lomholt , Ralf Metzler

We study the target search of interacting Brownian particles in a finite domain, focusing on the effect of inter-particle interactions on the search time. We derive the integral equation for the mean first-passage time and acquire its…

Statistical Mechanics · Physics 2023-07-12 Sunghan Ro , Juyeon Yi , Yong Woon Kim

Understanding how transcription factors (TFs) regulate mammalian gene expression in space and time is a central topic in biology. To activate a gene, a TF has first to diffuse in the available space of the nucleus until it reaches a target…

Subcellular Processes · Quantitative Biology 2018-11-19 Maxime Woringer , Xavier Darzacq

Response time and transcription level are vital parameters of gene regulation. They depend on how fast transcription factors (TFs) find and how efficient they occupy their specific target sites. It is well known that target site search is…

Biological Physics · Physics 2018-06-18 Johannes Hettich , J. Christof M. Gebhardt

DNA looping plays a fundamental role in a wide variety of biological processes, providing the backbone for long range interactions on DNA. Here we develop the first model for DNA looping by an arbitrarily large number of proteins and solve…

Subcellular Processes · Quantitative Biology 2007-05-23 Jose M. G. Vilar , Leonor Saiz

DNA replication fidelity is a critical issue in molecular biology. Biochemical experiments have provided key insights on the mechanism of fidelity control by DNAP in the past decades, whereas systematic theoretical studies on this issue…

Statistical Mechanics · Physics 2019-07-31 Qiu-Shi Li , Pei-Dong Zheng , Yao-Gen Shu , Zhong-Can Ou-Yang , Ming Li

Cellular responses often require the fast activation or repression of specific genes, which depends on Transcription Factors (TFs) that have to quickly find the promoters of these genes within a large genome. Transcription Factors (TFs)…

Subcellular Processes · Quantitative Biology 2015-09-02 Jérôme Cartailler , Jürgen Reingruber

This review examines intermittent target search strategies, which combine phases of slow motion, allowing the searcher to detect the target, and phases of fast motion during which targets cannot be detected. We first show that intermittent…

Statistical Mechanics · Physics 2015-05-27 O. Bénichou , C. Loverdo , M. Moreau , R. Voituriez

Strong experimental and theoretical evidence shows that transcription factors and other specific DNA-binding proteins find their sites using a two-mode search: alternating between 3D diffusion through the cell and 1D sliding along the DNA.…

Biomolecules · Quantitative Biology 2008-06-11 Zeba Wunderlich , Leonid A. Mirny

Cooperativity plays an important role in the action of proteins bound to DNA. A simple, mechanical mechanism for cooperativity, in the form of a tension-mediated interaction between proteins bound to DNA at two different locations is…

Soft Condensed Matter · Physics 2009-10-31 Joseph Rudnick , Robijn Bruinsma

Much of the natural variation for a complex trait can be explained by variation in DNA sequence levels. As part of sequence variation, gene-gene interaction has been ubiquitously observed in nature, where its role in shaping the development…

Applications · Statistics 2012-10-01 Shaoyu Li , Yuehua Cui

Proteins can locate their specific targets on DNA up to two orders of magnitude faster than the Smoluchowski three-dimensional diffusion rate. This happens due to non-specific adsorption of proteins to DNA and subsequent one-dimensional…

Soft Condensed Matter · Physics 2007-05-23 Tao Hu , B. I. Shklovskii

Molecular ecology uses molecular genetic data to answer traditional ecological questions in biogeography and biodiversity among others. Several ecological principles, such as the niche hypothesis and the competitive exclusions, are based on…

Interactions between proteins are hard to decipher. Protein-protein interactions are difficult problem to address because they are not based on differences in charge type like protein-DNA or protein-lipid interactions. In this manuscript we…

Statistical Mechanics · Physics 2013-12-31 Ognjen Perišić