DOCSLIB.ORG

Dynamic DNA Strand Displacement Circuits

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Dynamic DNA Strand Displacement Circuits Dynamic DNA Strand Displacement Circuits Thesis by David Yu Zhang In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy California Institute of Technology Pasadena, California 2010 (Defended May 14, 2010) c 2010 David Yu Zhang All Rights Reserved ii Acknowledgements When I started my graduate career–actually, even about one year before I finished my graduate career–I had no idea how anything I did would fit into a grander vision of science and technology. You see, a graduate student’s mark of success is somewhat different from a professor’s: A grad student’s good day is to get his data to agree with his data from yesterday, and to get both to agree with his model (after some model tinkering). A professor’s good day is to get his funding agency to agree with his research, and to get the world to agree with his genius. For me, after a somewhat lengthy undergrad detour into transcriptional circuitry work, I had figured out the trick to being a successful graduate student: work with the simplest, most well-understood system possible, and work around anything you don’t understand. I think my adviser, Erik Winfree, partially realized what I was doing, and started nagging me from fairly early on to develop a “deeper understanding” of the science that I did, and also to confront rather than avoid some of the harder problems. It wasn’t easy (as testified by the 2 and a half years it took to write the manuscript in chapter 2), but in the end I feel more like a scientist than a lab technician because of the experience. So, it is with great humbleness and appreciation that I first give thanks to my Ph.D. adviser, Erik Winfree. Paul Rothemund, Rebecca Schulman, and Jongmin Kim have provided me with invalu- able advice, both scientific and personal, and I feel that I would not be where I am today without their assistance. Paul inspired me to deal with my own adversities with poise by relating to me his past troubles, as well as the ways he dealt with them. Rebecca was and is an endless source of useful information, advice, and encouragement–she was the one who encouraged me to apply for the Hertz despite my undergrad GPA, and she is the one who helped me regain my self confidence in the last few turbulent years of my undergraduate education. Jongmin acted as my SURF co-mentor when I was an undergrad, and taught iii me a number of techniques, both in science and in Starcraft. All three of you were great advisers to me, and I am sure all of your future students will feel the same! I thank my research collaborators, Bernard Yurke, Andrew Turberfield, Georg Seelig, David Soloveichik, Rizal Hariadi, and Lulu Qian. Working with you all has been a wonderful and enlightening experience, and I look forward to future work together. I thank my other labmates, Nadine Dabby, Joseph Schaeffer, Peng Yin, and Sungwook Woo. Lab would be a much more boring place without your presence. I give special thanks to Karolyn Knoll, our administrative assistant, for making day-to- day life about a hundred times easier. Thank you Karolyn, for your help ordering reagents and fixing machines and scheduling travel and so on, and thank you for the cookies. Siping Han, Robert Barish, and Xiaoyan Robert Bao have been three of my best friends during my time here at Caltech, and I thank them for providing not only amusing personal stories, but also intelligent minds that I could bounce ideas off. I am confident that they will become great scientists, and look forward to talking to and working with them in the future. I thank Niles Pierce, Richard Murray, Zhen-Gang Wang, Scott Fraser, Joel Burdick, and Shuki Bruck, the members of my thesis committee, for their guidance. At the time, I wasn’t so happy that they assigned me three whole textbooks to read (and to be honest, I only finished one of them), but in retrospect, I agree that this was important for my development as a scientist. I am very grateful to the Fannie and John Hertz Foundation, not only for providing me with a nice stipend, but more importantly for providing me with a community of peers who are as excited by science and technology as I am. No other organization I belong to or know of has a stronger sense of unity, and I am proud to be a Hertz Fellow. My father, mother, and little sister Wendy deserve special thanks for putting up with me as long as they have. I am terrible at keeping in touch at a distance, and it is only through their tireless effort that I still feel that I have a family. Finally, I would like to thank my fiancee Sherry Xi Chen, who has made me a much happier man in the three years since we met. iv Abstract Nucleic acids, the “NA” in DNA and RNA, have long been known to be vitally important molecules within biological cells and organisms. However, they are interesting for more than just their known roles in biology: their predictable Watson-Crick base pairing properties allow nucleic acids to be powerful nanoscale engineering tools. Additionally, nucleic acid- based devices are particularly attractive as biotechnological tools, because nucleic acids naturally exist within all life, and thus nucleic acid devices more easily function in cellular environments. It is for these reasons that nucleic acids have emerged as a frequent star in recent synthetic biology, biotechnology, and nanotechnology research papers. This thesis is a collection of 6 experimental papers, 3 theoretical papers, and 1 review paper that demonstrate and characterize novel nucleic acid-based devices such as catalysts, logic gates, and allosteric switches. Particular effort was placed in ensuring that all the designs are generalizable in sequence and that all the devices are modular in nature; this allows many different components to be integrated into higher-complexity devices. The works presented in this thesis were designed using only non-covalent changes to nucleic acid complexes and structures via Watson-Crick base pairing–i.e. hybridization, branch migration, and dissociation. These three primitives are sufficient to construct an endless variety of circuits and devices, much like how resistors, capacitors, and inductors al- low complex electrical circuits. One advantage of devices, reactions, and circuits engineered using only Watson-Crick interactions is their robustness to their environmental conditions. While enzymatic reactions require specific temperatures, salt conditions, and co-factors, nucleic acid hybridization works reliably in a variety of different solutions. These works are not meant to be final, optimized designs for devices, but rather demon- strations of the wide range of possibilities afforded by nucleic acid engineering and of prob- lems that can be practically solved with dynamic nucleic acid devices in the near future. v Contents Acknowledgements iii Abstract v 1. DNA as an Engineering Material 1 2. A Survey of the Field 14 3. Kinetics of Strand Displacement Reactions 42 4. Amplification and Transduction of DNA Signals 95 5. Robustness and Specificity of the DNA Catalyst 132 6. Allosteric Control 166 7. Digital Nucleic Acid Concentration Sensor 181 8. Characterizing Cooperative Hybridization 203 9. Fixed Gain and Linear Classification 227 10. Towards Self Replication 243 A1. Domain-based Sequence Design of DNA 263 vi Chapter 1: DNA as an Engineering Material Author’s Note: This chapter is a semi-technical introduction to DNA for the general reader. For the technical reader, a review of the field is presented in Chapter 2. For better or for worse, DNA biology and technology possess more lay recognition than most other sciences. Humanity’s ancient and general fascination with the heredity of traits almost guaranteed that genetics would blossom as a center-stage scientific discipline even before the structure of DNA was fully unraveled. In recent times, DNA has been popularized by films such as Jurassic Park, and nowadays most public high school curricula teach of DNA being the “master molecule of the cell.” Given the scope and promise of DNA biotechnology, it should come as no surprise that technical improvements are improving at a rate as fast as or faster than improvements in the other great technology of our lifetime–silicon transistors. In a rough equivalent of Moore’s Law, the prices of DNA synthesis and sequencing are dropping exponentially in time (Fig. 1-1). What does come as a surprise to most who hear about my research for the first time, is the fact that I and others in my field are using DNA quite differently than the way it is used in biology. Geneticists and microbiologists primarily use synthetic DNA as a method of granting a cell the blueprints for constructing a protein that the cell would otherwise not have, using the cellular machinery for transcription and translation to process the introduced DNA. We biomolecular engineers instead use DNA as a basic programmable 1 FIG. 1-1: Carlson’s Law. The price of DNA oligonucleotide and gene synthesis has been dropping exponentially over the past 20 years. Image by Robert Carlson, http://www.synthesis.cc/2008/11/gene- synthesis-cost-update.html. building block, with which we can build all sorts of useful and complex devices at the nanoscale, independent of the cell’s mechanisms. The use of naturally existing objects in ways different than their natural use is hardly a new concept; this idea dates back as far as the Stone Age, when humans used the bones of dead animals for axes and other tools.
Load more

Recommended publications
  • Design of Nucleic Acid Strands with Long Low-Barrier Folding Pathways
    Nat Comput DOI 10.1007/s11047-016-9587-9 Design of nucleic acid strands with long low-barrier folding pathways Anne Condon1 · Bonnie Kirkpatrick2 · Ján Maˇnuch1 © The Author(s) 2017. This article is published with open access at Springerlink.com Abstract A major goal of natural computing is to design fully developed, that exploit base pairing interactions of biomolecules, such as nucleic acid sequences, that can be nucleic acids. Prominent examples include DNA strand dis- used to perform computations. We design sequences of placement systems (DSDs) (Seelig et al. 2006) and RNA nucleic acids that are “guaranteed” to have long folding origami systems (Geary and Andersen 2014). Our work here pathways relative to their length. This particular sequences is motivated by the goal of computing with a single RNA with high probability follow low-barrier folding pathways sequence as the nucleic acids of the sequence interact with that visit a large number of distinct structures. Long fold- each other. ing pathways are interesting, because they demonstrate that RNA sequences form folded structures in which pairs of natural computing can potentially support long and com- nucleic acids biochemically bond to each other. These bonds plex computations. Formally, we provide the first scalable change the physical energy of the sequence, and a given designs of molecules whose low-barrier folding pathways, sequence prefers to assume low-energy folded structures. with respect to a simple, stacked pair energy model, grow Folding is a dynamic process, constrained by kinetics, dur- superlinearly with the molecule length, but for which all sig- ing which an RNA sequence will move through a sequence nificantly shorter alternative folding pathways have an energy of structures with each differing from the previous one by barrier that is 2 − times that of the low-barrier pathway for the addition or removal of a single base pair.
    [Show full text]
  • Algorithms for Nucleic Acid Sequence Design
    Algorithms for Nucleic Acid Sequence Design Thesis by Joseph N. Zadeh In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy California Institute of Technology Pasadena, California 2010 (Defended December 8, 2009) ii © 2010 Joseph N. Zadeh All Rights Reserved iii Acknowledgements First and foremost, I thank Professor Niles Pierce for his mentorship and dedication to this work. He always goes to great lengths to make time for each member of his research group and ensures we have the best resources available. Professor Pierce has fostered a creative environment of learning, discussion, and curiosity with a particular emphasis on quality. I am grateful for the tremendously positive influence he has had on my life. I am fortunate to have had access to Professor Erik Winfree and his group. They have been very helpful in pushing the limits of our software and providing fun test cases. I am also honored to have two other distinguished researchers on my thesis committee: Stephen Mayo and Paul Rothemund. All of the work presented in this thesis is the result of collaboration with extremely talented individuals. Brian Wolfe and I codeveloped the multiobjective design algorithm (Chapter 3). Brian has also been instru- mental in finessing details of the single-complex algorithm (Chapter 2) and contributing to the parallelization of NUPACK’s core routines. I would also like to thank Conrad Steenberg, the NUPACK software engineer (Chapter 4), who has significantly improved the performance of the site and developed robust secondary structure drawing code. Another codeveloper on NUPACK, Justin Bois, has been a good friend, mentor, and reliable coding partner.
    [Show full text]
  • A Global Sampling Approach to Designing and Reengineering RNA
    i “rnaensign” — 2017/7/1 — 22:02 — page 1 — #1 i i i Published online ?? Nucleic Acids Research, ??, Vol. ??, No. ?? 1–11 doi:10.1093/nar/gkn000 Aglobalsamplingapproachtodesigningandreengineering RNA secondary structures 1,2, 1, 3 1 1 Alex Levin ⇤,MieszkoLis ⇤,YannPonty ,CharlesW.O’Donnell ,SrinivasDevadas , 1,2, 1,2,4, Bonnie Berger †,J´erˆomeWaldisp¨uhl † 1 Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA. and 2 Department of Mathematics, MIT, Cambridge, MA 02139, USA. and 3 Laboratoire d’Informatique, Ecole´ Polytechnique, Palaiseau, France. and 4 School of Computer Science, McGill University, Montreal, QC H2A 3A7, Canada. Received ??; Revised ??; Accepted ?? ABSTRACT mechanisms (1), reprogramming cellular behavior (2), and designing logic circuits (3). The development of algorithms for designing artificial Here, we aim to design RNA sequences that fold into RNA sequences that fold into specific secondary structures specific secondary structures (a.k.a. inverse folding). Even has many potential biomedical and synthetic biology in this case, efficient computational formulations remain applications. To date, this problem remains computationally difficult, with no exact solutions known. Instead, the solutions difficult, and current strategies to address it resort available today rely on local search strategies and heuristics. to heuristics and stochastic search techniques. The Indeed, the computational difficulty of the RNA design most popular methods consist of two steps: First a problem was proven by M. Schnall-Levin et al. (4). random seed sequence is generated; next, this seed is One of the first and most widely known programs for progressively modified (i.e. mutated) to adopt the desired the RNA inverse folding problem is RNAinverse (5).
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7.058,515 B1 Selifonov Et Al
    US007058515B1 (12) United States Patent (10) Patent No.: US 7.058,515 B1 Selifonov et al. (45) Date of Patent: *Jun. 6, 2006 (54) METHODS FOR MAKING CHARACTER (56) References Cited STRINGS, POLYNUCLEOTIDES AND POLYPEPTIDES HAVING DESRED CHARACTERISTICS U.S. PATENT DOCUMENTS 4.959,312 A 9, 1990 Sirokin (75) Inventors: Sergey A. Selifonov, Los Altos, CA 4,994,379 A 2/1991 Chang (US); Willem P. C. Stemmer, Los 5,023,171 A 6, 1991 Ho et al. ....................... 435/6 Gatos, CA (US); Claes Gustafsson, 5,043,272 A 8/1991 Hartly et al. Belmont, CA (US); Matthew Tobin, 5,066,584 A 11/1991 Gyllensten et al. San Jose, CA (US); Stephen del 5,264,563 A 11/1993 Huse Cardayre, Belmont, CA (US); Phillip SE A Rhen A. Patten, Menlo Park, CA (US); 3.) A 96 MTS al. Jeremy Minshull, Menlo Park, CA 5.512.463 A 4/1996 Stemmer ................... 435,912 (US); Lorraine J. Giver, Sunnyvale, 5.514.588 A 5/1996 Varadaraj.................... 435/262 CA (US) 5,519,319 A 5/1996 Smith et al. 5,521,077 A 5/1996 Kholsa et al. (73) Assignee: Maxygen, Inc., Redwood City, CA 5,565,350 A 10, 1996 Kmiec (US) 5,580,730 A 12/1996 Okamoto 5,605,793 A 2/1997 Stemmer ....................... 435/6 (*) Notice: Subject to any disclaimer, the term of this 5,612.205 A 3/1997 Kay et al. patent is extended or adjusted under 35 3. 6. 3. Site U.S.C. 154(b) by 0 days. 5,717,085w - A 2f1998 Little et al.a This patent is Subject to a terminal dis- 29, Stil 435/6 claimer.
    [Show full text]
  • Nanoparticle‐Mediated DNA and Mrna Delivery
    REVIEW www.advhealthmat.de Next-Generation Vaccines: Nanoparticle-Mediated DNA and mRNA Delivery William Ho, Mingzhu Gao, Fengqiao Li, Zhongyu Li, Xue-Qing Zhang,* and Xiaoyang Xu* organism-based vaccines have wiped out or Nucleic acid vaccines are a method of immunization aiming to elicit immune nearly eradicated many once great killers responses akin to live attenuated vaccines. In this method, DNA or messenger of humanity, including smallpox, polio, RNA (mRNA) sequences are delivered to the body to generate proteins, which measles, mumps, rubella, diphtheria, per- [1–4] mimic disease antigens to stimulate the immune response. Advantages of tussis, and tetanus. However, the quick emergence of diseases such as SARS- nucleic acid vaccines include stimulation of both cell-mediated and humoral CoV-2, H1N1 as well as quickly evolving immunity, ease of design, rapid adaptability to changing pathogen strains, and deadly diseases like Ebola create a challenge customizable multiantigen vaccines. To combat the SARS-CoV-2 pandemic, for conventional vaccines such as live at- and many other diseases, nucleic acid vaccines appear to be a promising tenuated viral vaccines (LAV), and inacti- [5,6] method. However, aid is needed in delivering the fragile DNA/mRNA payload. vated/killed viral vaccines, which with Many delivery strategies have been developed to elicit effective immune the traditional vaccine development path- way may take on average over 10 years to stimulation, yet no nucleic acid vaccine has been FDA-approved for human develop, or with Ebola requiring an acceler- use. Nanoparticles (NPs) are one of the top candidates to mediate successful ated 5-year development,[7] and even more DNA/mRNA vaccine delivery due to their unique properties, including time needed to scale up manufacturing and unlimited possibilities for formulations, protective capacity, simultaneous stockpile for a large country.
    [Show full text]
  • A Rule-Based Modelling and Simulation Tool for DNA Strand Displacement Systems
    This is an electronic reprint of the original article. This reprint may differ from the original in pagination and typographic detail. Gautam, Vinay; Long, Shiting; Orponen, Pekka RuleDSD: A rule-based modelling and simulation tool for DNA strand displacement systems Published in: Proceedings of the 13th International Joint Conference on Biomedical Engineering Systems and Technologies DOI: 10.5220/0008979101580167 Published: 01/01/2020 Document Version Peer reviewed version Published under the following license: CC BY-NC-ND Please cite the original version: Gautam, V., Long, S., & Orponen, P. (2020). RuleDSD: A rule-based modelling and simulation tool for DNA strand displacement systems. In E. De Maria, A. Fred, & H. Gamboa (Eds.), Proceedings of the 13th International Joint Conference on Biomedical Engineering Systems and Technologies: Volume 3 BIOINFORMATICS (pp. 158-167) https://doi.org/10.5220/0008979101580167 This material is protected by copyright and other intellectual property rights, and duplication or sale of all or part of any of the repository collections is not permitted, except that material may be duplicated by you for your research use or educational purposes in electronic or print form. You must obtain permission for any other use. Electronic or print copies may not be offered, whether for sale or otherwise to anyone who is not an authorised user. Powered by TCPDF (www.tcpdf.org) RuleDSD: A Rule-based Modelling and Simulation Tool for DNA Strand Displacement Systems Vinay Gautam a, Shiting Long and Pekka Orponen b Department of Computer Science, Aalto University, 00076 Aalto, Finland fvinay.gautam, shiting.long, pekka.orponeng@aalto.fi Keywords: DNA Strand Displacement, DSD Modelling and Simulation, PySB, Rule-based Model, BioNetGen.
    [Show full text]
  • Design of Nucleic Acid Sequences for DNA Computing Based on a Thermodynamic Approach
    Title Design of nucleic acid sequences for DNA computing based on a thermodynamic approach Author(s) Tanaka, Fumiaki; Kameda, Atsushi; Yamamoto, Masahito; Ohuchi, Azuma Nucleic Acids Research, 33(3), 903-911 Citation https://doi.org/10.1093/nar/gki235 Issue Date 2005 Doc URL http://hdl.handle.net/2115/64504 Type article File Information gki235.pdf Instructions for use Hokkaido University Collection of Scholarly and Academic Papers : HUSCAP Published online February 8, 2005 Nucleic Acids Research, 2005, Vol. 33, No. 3 903–911 doi:10.1093/nar/gki235 Design of nucleic acid sequences for DNA computing based on a thermodynamic approach Fumiaki Tanaka1,*, Atsushi Kameda2, Masahito Yamamoto1,2 and Azuma Ohuchi1,2 1Graduate School of Engineering, Hokkaido University, North 13, West 8, Kita-ku, Sapporo 060-8628, Japan and 2CREST, Japan Science and Technology Corporation, 4-1-8, Honmachi, Kawaguchi, Saitama, 332-0012, Japan Received October 19, 2004; Revised and Accepted January 20, 2005 ABSTRACT order to satisfy the constraints based on the physicochemical properties of nucleic acids. In particular, it is essential to We have developed an algorithm for designing prevent undesired hybridization. In DNA computing, multiple multiple sequences of nucleic acids that have a sequences need to be designed that do not hybridize non- uniform melting temperature between the sequence specifically with each other (10,11), while in RNA secondary and its complement and that do not hybridize non- structure design, a single sequence needs to be designed that specifically with each other based on the minimum folds into the desired secondary structure (12–15). For free energy (DGmin).
    [Show full text]
  • 2013 CIRC Poster Session Abstracts
    3rd Annual Center for Integrated Research Computing Poster Session! May 10, 2013 2013 Annual Poster Session ! 1 3rd Annual Center for Integrated Research Computing Poster Session! May 10, 2013 Computational Design and Characterization of 2-D tendency to cross- and self-hybridize. These features are observed in Photonic Crystal Geometries for Biosensing RNA sequences with known structure. We demonstrate that pre- James E. Baker and Benjamin L. Miller selected sequences accelerate the design of structures that are mimics Physics and Astronomy of biologically relevant structures. This is implemented as a new Dermatology structure design component of RNAstructure (http:// Biochemistry and Biophysics rna.urmc.rochester.edu/RNAstructure.html). This work is a Biomedical Engineering collaboration with Celadon Laboratories, Inc. (http:// The importance of early disease diagnosis both for initiating www.celadonlabs.com/). successful clinical treatment and preventing disease transmission continues to drive the development of rapid, ultrasensitive, label-free Next Generation Sequence Analysis of the Transcriptional biosensors. Sensors based on two-dimensional photonic bandgap Response to Neonatal Hyperoxia crystal structures, in particular, have the potential for single- Soumyaroop Bhattacharya, Chin-Yi Chu, Zhongyang Zhou, Min Yee, pathogen detection capabilities. In order to achieve such high Ashley M. Lopez, Valerie A. Lunger, Bradley Buczynski, Gloria S. sensitivity, the geometric structure of the photonic crystal must be Pryhuber, Michael A. O’Reilly, and Thomas J. Mariani designed in a way that pathogen binding is evident in the optical Pediatrics transmission spectrum of the crystal. Computational modeling methods allow us to simulate the electric field profiles and Rationale: Bronchopulmonary Dysplasia (BPD) is a major transmission spectra that we expect to observe for different photonic complication of preterm birth associated with significant morbidity.
    [Show full text]
  • Computer-Aided Design Software for Custom Nucleic Acid Nanostructures
    Aalto University School of Science Degree Programme in Computer Science and Engineering Juhana Kommeri Computer-aided design software for cus- tom nucleic acid nanostructures Master's Thesis Espoo, October 2, 2016 Supervisors: Professor Mauri Kostiainen Advisor: Ph.D., Docent Veikko Linko Aalto University School of Science ABSTRACT OF Degree Programme in Computer Science and Engineering MASTER'S THESIS Author: Juhana Kommeri Title: Computer-aided design software for custom nucleic acid nanostructures Date: October 2, 2016 Pages: 72 Major: Media technology Code: T-111 Supervisors: Professor Mauri Kostiainen Advisor: Ph.D., Docent Veikko Linko The past decade has witnessed significant improvement in the techniques for as- sembling nucleic acid molecules into desired nanostructures. Today, structural DNA nanotechnology is seen as an attractive field by many multidisciplinary researchers who are impressed on the ability to position and control molecules with nanometer-level accuracy. The rationally designed DNA structures possess a tremendous potential in many bionanotechnological applications, and therefore the complexity of the designed structures is constantly increasing. To follow this trend and to enable straightforward design of such structures, powerful and ver- satile computer-aided design software and simulation tools are urgently needed. In this thesis various design software for creating nucleic acid nanostructures are assessed against predefined criteria. Using these software, exemplary DNA designs are created, and the features of the software are described. The aim of this comparison is to give a comprehensive overview of the currently available software and help a reader to decide which software to use for each particular purpose. In addition, a specific plugin for the most commonly used software caDNAno is created.
    [Show full text]
  • Principles and Applications of Nucleic Acid Strand Displacement Reactions † ‡ † Friedrich C
    Review Cite This: Chem. Rev. XXXX, XXX, XXX−XXX pubs.acs.org/CR Principles and Applications of Nucleic Acid Strand Displacement Reactions † ‡ † Friedrich C. Simmel,*, Bernard Yurke,*, and Hari R. Singh † Physics Department, TU München, 85748 Garching, Germany ‡ Micron School of Materials Science and Engineering, Boise State University, Boise, ID 83725, United States ABSTRACT: Dynamic DNA nanotechnology, a subfield of DNA nanotechnology, is concerned with the study and application of nucleic acid strand-displacement reactions. Strand-displacement reactions generally proceed by three-way or four-way branch migration and initially were investigated for their relevance to genetic recombination. Through the use of toeholds, which are single-stranded segments of DNA to which an invader strand can bind to initiate branch migration, the rate with which strand displacement reactions proceed can be varied by more than 6 orders of magnitude. In 6 (UTC). addition, the use of toeholds enables the construction of enzyme-free DNA reaction networks exhibiting complex dynamical behavior. A demonstration of this was provided in the year 2000, in which strand displacement reactions were employed to drive a DNA- based nanomachine (Yurke, B.; et al. Nature 2000, 406, 605−608). Since then, toehold- mediated strand displacement reactions have been used with ever increasing sophistication and the field of dynamic DNA nanotechnology has grown exponentially. Besides molecular o legitimately share published articles. machines, the field has produced enzyme-free catalytic systems, all DNA chemical oscillators and the most complex molecular computers yet devised. Enzyme-free catalytic systems can function as chemical amplifiers and as such have received considerable attention for sensing and detection applications in chemistry and medical diagnostics.
    [Show full text]
  • Control of RNA Function by Conformational Design
    DISSERTATION / DOCTORAL THESIS Titel der Dissertation /Title of the Doctoral Thesis Control of RNA function by conformational design verfasst von / submitted by Mag. rer. nat. Stefan Badelt angestrebter akademischer Grad / in partial fulfilment of the requirements for the degree of Doctor of Philosophy (PhD) Wien, 2016 / Vienna, 2016 Studienkennzahl lt. Studienblatt / A 794 685 490 degree programme code as it appears on the student record sheet: Dissertationsgebiet lt. Studienblatt / Molekulare Biologie field of study as it appears on the student record sheet: Betreut von / Supervisor: Univ.-Prof. Dipl.-Phys. Dr. Ivo Hofacker Design landscapes >Output Input AGGAACAGUCGCACU ACCCACCUCGACAUC AGCAACA GUAAAUCAAAUUGGA AGGAUCU ACUGAAGCCCUUGGU AGGAUCA CUGGAGUCACCAGGG objective function AGGAACA GGUUUACGUACUACU design Energy landscapes 0.7 0.7 >Input -8.0 Output 3.9 3.7 1.1 2.8 1.2 1.3 2.3 0.8 AGGAACAGUCGCACU 3.5 2.6 2.6 2.8 3.9 2.3 -10.0 3.0 4.2 1.2 0.7 2.3 1.2 4.4 1.3 0.599999 1.3 2.4 1.0 0.8 100 1.5 2.0 1.2 0.8 97 98 99 2.8 1.4 1.0 94 95 93 96 92 2.3 0.7 2.6 0.8 91 1.5 1.3 2.0 2.6 1.6 89 90 1.9 0.8 2.0 86 88 87 2.9 2.3 1.9 1.3 1.3 ACCCACCUCGACAUC 0.6 83 85 84 82 2.6 1.0 0.8 0.8 77 81 79 78 80 0.7 76 1.9 74 75 73 1.5 72 0.7 -12.0 0.8 0.8 70 71 1.1 0.799999 1.2 0.8 69 68 0.8 0.8 0.8 63 65 64 66 67 0.9 1.2 1.2 59 60 58 61 62 1.2 1.4 1.7 1.2 55 54 57 56 3.1 3.0 4.2 52 53 51 49 50 0.7 1.0 45 44 46 47 48 42 43 41 3.5 1.0 38 39 40 1.3 0.6 2.6 1.3 0.8 0.8 0.8 GUAAAUCAAAUUGGA 37 35 36 34 32 33 31 30 28 29 27 1.2 0.8 24 25 26 23 -14.0 22 20 21 2.4 17
    [Show full text]
  • Biomolecular Modeling and Simulation: a Prospering Multidisciplinary Field
    Annual Review of Biophysics Biomolecular Modeling and Simulation: A Prospering Multidisciplinary Field Tamar Schlick,1,2,3 Stephanie Portillo-Ledesma,1 Christopher G. Myers,1 Lauren Beljak,4 Justin Chen,4 Sami Dakhel,4 Daniel Darling,4 Sayak Ghosh,4 Joseph Hall,4 Mikaeel Jan,4 Emily Liang,4 Sera Saju,4 Mackenzie Vohr,4 Chris Wu,4 Yifan Xu,4 and Eva Xue4 1Department of Chemistry, New York University, New York, New York 10003, USA; email: [email protected] 2Courant Institute of Mathematical Sciences, New York University, New York, New York 10012, USA 3New York University–East China Normal University Center for Computational Chemistry, New York University Shanghai, Shanghai 200122, China 4College of Arts and Science, New York University, New York, New York 10003, USA Annu. Rev. Biophys. 2021. 50:267–301 Keywords First published as a Review in Advance on biomolecular modeling, biomolecular simulation, biomolecular dynamics, February 19, 2021 structure prediction, protein folding, DNA folding, RNA folding, The Annual Review of Biophysics is online at multiscale modeling, citizen science projects, machine learning, artificial biophys.annualreviews.org intelligence https://doi.org/10.1146/annurev-biophys-091720- 102019 Abstract Copyright © 2021 by Annual Reviews. We reassess progress in the field of biomolecular modeling and simulation, Annu. Rev. Biophys. 2021.50:267-301. Downloaded from www.annualreviews.org All rights reserved following up on our perspective published in 2011. By reviewing metrics Access provided by New York University - Bobst Library on 05/12/21. For personal use only. for the field’s productivity and providing examples of success, we under- score the productive phase of the field, whose short-term expectations were overestimated and long-term effects underestimated.
    [Show full text]