A5025227332- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- Bacteriophages and microbial interactions
- RNA Interference and Gene Delivery
- Gene Regulatory Network Analysis
- RNA and protein synthesis mechanisms
- Advanced Thermodynamics and Statistical Mechanics
- Molecular Junctions and Nanostructures
- Neural dynamics and brain function
- Quantum Computing Algorithms and Architecture
- Protein Structure and Dynamics
- CRISPR and Genetic Engineering
- Advanced Memory and Neural Computing
- Machine Learning in Materials Science
- Spectroscopy and Quantum Chemical Studies
- Molecular Communication and Nanonetworks
- Photoreceptor and optogenetics research
- DNA and Biological Computing
- Origins and Evolution of Life
- Evolution and Genetic Dynamics
- Advanced Polymer Synthesis and Characterization
- Modular Robots and Swarm Intelligence
- Polymer crystallization and properties
- Quantum-Dot Cellular Automata
- Cancer Genomics and Diagnostics
Imperial College London
2016-2025
University of Oxford
2010-2018
Columbia University
2018
Ben-Gurion University of the Negev
2015
Interface (United Kingdom)
2015
Rockefeller University
2015
California Institute of Technology
2013
Abstract Dynamic DNA nanotechnology often uses toehold-mediated strand displacement for controlling reaction kinetics. Although the dependence of kinetics on toehold length has been experimentally characterized and phenomenologically modeled, detailed biophysical understanding remained elusive. Here, we study at multiple levels detail, using an intuitive model a random walk 1D energy landscape, secondary structure with single base-pair steps coarse-grained molecular that incorporates 3D...
We explore in detail the structural, mechanical and thermodynamic properties of a coarse-grained model DNA similar to that introduced Thomas E. Ouldridge, Ard A. Louis, Jonathan P.K. Doye, Phys. Rev. Lett. 104 178101 (2010). Effective interactions are used represent chain connectivity, excluded volume, base stacking hydrogen bonding, naturally reproducing range behaviour. quantify relation experiment thermodynamics single-stranded stacking, duplex hybridization hairpin formation, as well...
We introduce a sequence-dependent parametrization for coarse-grained DNA model [T. E. Ouldridge, A. Louis, and J. P. K. Doye, Chem. Phys. 134, 085101 (2011)]10.1063/1.3552946 originally designed to reproduce the properties of molecules with average sequences. The new introduces stacking base-pairing interaction strengths chosen melting temperatures short duplexes. By developing histogram reweighting technique, we are able fit our parameters thousands To demonstrate flexibility model, study...
We introduce an extended version of oxDNA, a coarse-grained model deoxyribonucleic acid (DNA) designed to capture the thermodynamic, structural, and mechanical properties single- double-stranded DNA. By including explicit major minor grooves by slightly modifying coaxial stacking backbone-backbone interactions, we improve ability treat large (kilobase-pair) structures, such as DNA origami, which are sensitive these geometric features. Further, extend model, was previously parameterised just...
We introduce a coarse-grained rigid nucleotide model of DNA that reproduces the basic thermodynamics short strands, duplex hybridization, single-stranded stacking, and hairpin formation, also captures essential structural properties DNA: helical pitch, persistence length, torsional stiffness double-stranded molecules, as well comparative flexibility unstacked single strands. apply to calculate detailed free-energy landscape one full cycle "tweezers," simple machine driven by hybridization...
While the thermodynamics of DNA hybridization is well understood, much less known about kinetics this classic system. Filling gap in our understanding has new urgency because nanotechnology often depends critically on binding rates. Here we use a coarse-grained model to explore oligomers, finding that strand association proceeds through complex set intermediate states. Successful events start with formation few metastable base-pairing interactions, followed by zippering remaining bonds....
To simulate long time and length scale processes involving DNA it is necessary to use a coarse-grained description. Here we provide an overview of different approaches such coarse graining, focussing on those at the nucleotide level that allow self-assembly associated with nanotechnology be studied. OxDNA, our recently-developed model, particularly suited this task, has opened up field systematic study by simulations. We illustrate some range systems which model being applied, as well...
We present a new, nucleotide-level model for RNA, oxRNA, based on the coarse-graining methodology recently developed oxDNA of DNA. The is designed to reproduce structural, mechanical and thermodynamic properties level aims retain relevant physics RNA hybridization structure single- double-stranded RNA. In order explore its strengths weaknesses, we test in range nanotechnological biological settings. Applications explored include folding thermodynamics pseudoknot, formation kissing loop...
In recent years experiments have demonstrated that living cells can measure low chemical concentrations with high precision, and much progress has been made in understanding what sets the fundamental limit to precision of sensing. Chemical concentration measurements start binding ligand molecules receptor proteins, which is an inherently noisy process, especially at concentrations. The signaling networks transmit information on from receptors into cell filter this input noise as possible....
By using oxDNA, a coarse-grained nucleotide-level model of DNA, we are able to directly simulate the self-assembly small 384-base-pair origami from single-stranded scaffold and staple strands in solution. In general, see attachment new occurring parallel, but with cooperativity evident for binding second domain if adjacent junction is already partially formed. For system exactly one copy each strand, observe complete assembly pathway an intermediate temperature window; at low temperatures...
The rupture of double-stranded DNA under stress is a key process in biophysics and nanotechnology. In this article, we consider the shear-induced short duplexes, system that has been given new importance by recently designed force sensors nanotechnological devices. We argue must be understood as an activated process, where duplex state metastable strands will separate finite time depends on length applied. Thus, critical shearing required to strongly scale observation. use simple models show...
Abstract Recent years have seen great advances in the development of synthetic self-assembling molecular systems. Designing out-of-equilibrium architectures, however, requires a more subtle control over thermodynamics and kinetics reactions. We propose mechanism for enhancing thermodynamic drive DNA strand-displacement reactions whilst barely perturbing forward reaction rates: introduction mismatches within initial duplex. Through combination experiment simulation, we demonstrate that...
Toehold-mediated strand displacement is the most abundantly used method to achieve dynamic switching in DNA-based nanotechnology. An "invader" binds "toehold" overhang of a target and replaces target-bound "incumbent" strand. Here, complementarity invader single-stranded toehold provides free energy bias reaction. Despite widespread use reactions for realizing DNA nanostructures, variants on basic motif have not been completely characterized. Here we introduce simple thermodynamic model,...
The relationship between the thermodynamic and computational properties of physical systems has been a major theoretical interest since at least 19th century. It also become increasing practical importance over last half-century as energetic cost digital devices exploded. Importantly, real-world computers obey multiple constraints on how they work, which affects their properties. Moreover, many these apply to both naturally occurring computers, like brains or Eukaryotic cells, systems. Most...
Can a micron-sized sack of interacting molecules autonomously learn an internal model complex and fluctuating environment? We draw insights from control theory, machine learning chemical reaction network theory statistical physics to develop general architecture whereby broad class systems can distributions. Our construction takes the form implementation learning’s optimization workhorse: gradient descent on relative entropy cost function, which we demonstrate be viewed as integral feedback...
DNA has enormous potential as a programmable material for creating artificial nanoscale structures and devices. For more complex systems, however, rational design optimization can become difficult. We have recently proposed coarse-grained model of that captures the basic thermodynamic, structural, mechanical changes associated with fundamental process in much nanotechnology, formation duplexes from single strands. In this article, we demonstrate provide powerful insight into operation...
Both computers and living cells copy information, but doing so comes at a cost of energy. A new theoretical analysis shows that biological systems come close to do not reach the predicted lower bound on this energy, increases as copying becomes more accurate.
Abstract We predict a novel conformational regime for DNA, where denaturation bubbles form at the tips of plectonemes and study its properties using coarse-grained simulations. For negative supercoiling, this lies between bubble-dominated plectoneme-dominated phases explains broad transition two observed in experiment. Tip cause localisation within thermodynamically weaker AT-rich sequences can greatly suppress plectoneme diffusion by pinning mechanism. They occur supercoiling densities...
We use a recently developed coarse-grained model to simulate the overstretching of duplex DNA. Overstretching at 23C occurs 74 pN in model, about 6-7 higher than experimental value equivalent salt conditions. Furthermore, reproduces temperature dependence force well. The mechanism is always force-induced melting by unpeeling from free ends. That we never see S-DNA (overstretched DNA), even though there clear evidence for this mode under certain conditions, suggests that not simply an...
During the last decade coarse-grained nucleotide models have emerged that allow us to study DNA and RNA on unprecedented time length scales. Among them is oxDNA, a coarse-grained, sequence-specific model captures hybridisation transition of many structural properties single- double-stranded DNA. oxDNA was previously only available as standalone software, but has now been implemented into popular LAMMPS molecular dynamics code. This article describes new implementation analyses its parallel...
In nucleic acid nanotechnology, strand displacement is a widely used mechanism where one from hybridized duplex exchanged with an invading that binds to toehold, single-stranded region on the duplex. It perform logic operations molecular level, initiate cascaded reactions, or even for in vivo diagnostics and treatments. While systematic experimental studies have been carried out probe kinetics of DNA different toehold lengths, sequences, mismatch positions, there has not comparable...