Protein Preliminaries and Structure Prediction Fundamentals For
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Algorithms & Experiments for the Protein
ALGORITHMS & EXPERIMENTS FOR THE PROTEIN CHAIN LATTICE FITTING PROBLEM DALLAS THOMAS Bachelor of Science, University of Lethbridge, 2004 Bachelor of Science, Kings University College, 2002 A Thesis Submitted to the School of Graduate Studies of the University of Lethbridge in Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE Department of Mathematics and Computer Science University of Lethbridge LETHBRIDGE, ALBERTA, CANADA c Dallas Thomas, 2006 Abstract This study seeks to design algorithms that may be used to determine if a given lattice is a good approximation to a given rigid protein structure. Ideal lattice models discovered using our techniques may then be used in algorithms for protein folding and inverse protein folding. In this study we develop methods based on dynamic programming and branch and bound in an effort to identify “ideal” lattice models. To further our understanding of the concepts behind the methods we have utilized a simple cubic lattice for our analysis. The algorithms may be adapted to work on any lattice. We describe two algorithms. One for aligning the protein backbone to the lattice as a walk. This algorithm runs in polynomial time. The sec- ond algorithm for aligning a protein backbone as a path to the lattice. Both the algorithms seek to minimize the CRMS deviation of the alignment. The second problem was recently shown to be NP-Complete, hence it is highly unlikely that an efficient algorithm exists. The first algorithm gives a lower bound on the optimal solution to the second problem, and can be used in a branch and bound procedure. -
Resource-Efficient Quantum Algorithm for Protein Folding
www.nature.com/npjqi ARTICLE OPEN Resource-efficient quantum algorithm for protein folding ✉ Anton Robert1,2, Panagiotis Kl. Barkoutsos 1, Stefan Woerner 1 and Ivano Tavernelli 1 Predicting the three-dimensional structure of a protein from its primary sequence of amino acids is known as the protein folding problem. Due to the central role of proteins’ structures in chemistry, biology and medicine applications, this subject has been intensively studied for over half a century. Although classical algorithms provide practical solutions for the sampling of the conformation space of small proteins, they cannot tackle the intrinsic NP-hard complexity of the problem, even when reduced to the simplest Hydrophobic-Polar model. On the other hand, while fault-tolerant quantum computers are beyond reach for state-of- the-art quantum technologies, there is evidence that quantum algorithms can be successfully used in noisy state-of-the-art quantum computers to accelerate energy optimization in frustrated systems. In this work, we present a model Hamiltonian with OðN4Þ scaling and a corresponding quantum variational algorithm for the folding of a polymer chain with N monomers on a lattice. The model reflects many physico-chemical properties of the protein, reducing the gap between coarse-grained representations and mere lattice models. In addition, we use a robust and versatile optimization scheme, bringing together variational quantum algorithms specifically adapted to classical cost functions and evolutionary strategies to simulate the folding of the 10 amino acid Angiotensin on 22 qubits. The same method is also successfully applied to the study of the folding of a 7 amino acid neuropeptide using 9 qubits on an IBM 20-qubit quantum computer. -
Annual Scientific Report 2013 on the Cover Structure 3Fof in the Protein Data Bank, Determined by Laponogov, I
EMBL-European Bioinformatics Institute Annual Scientific Report 2013 On the cover Structure 3fof in the Protein Data Bank, determined by Laponogov, I. et al. (2009) Structural insight into the quinolone-DNA cleavage complex of type IIA topoisomerases. Nature Structural & Molecular Biology 16, 667-669. © 2014 European Molecular Biology Laboratory This publication was produced by the External Relations team at the European Bioinformatics Institute (EMBL-EBI) A digital version of the brochure can be found at www.ebi.ac.uk/about/brochures For more information about EMBL-EBI please contact: [email protected] Contents Introduction & overview 3 Services 8 Genes, genomes and variation 8 Molecular atlas 12 Proteins and protein families 14 Molecular and cellular structures 18 Chemical biology 20 Molecular systems 22 Cross-domain tools and resources 24 Research 26 Support 32 ELIXIR 36 Facts and figures 38 Funding & resource allocation 38 Growth of core resources 40 Collaborations 42 Our staff in 2013 44 Scientific advisory committees 46 Major database collaborations 50 Publications 52 Organisation of EMBL-EBI leadership 61 2013 EMBL-EBI Annual Scientific Report 1 Foreword Welcome to EMBL-EBI’s 2013 Annual Scientific Report. Here we look back on our major achievements during the year, reflecting on the delivery of our world-class services, research, training, industry collaboration and European coordination of life-science data. The past year has been one full of exciting changes, both scientifically and organisationally. We unveiled a new website that helps users explore our resources more seamlessly, saw the publication of ground-breaking work in data storage and synthetic biology, joined the global alliance for global health, built important new relationships with our partners in industry and celebrated the launch of ELIXIR. -
Doctor of Philosophy
Protein structure recognition: From eigenvector analysis to structural threading method by Haibo Cao A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Condensed Matter Physics Program of Study Committee: Kai-Ming Bo, Major Professor Drena Dobbs Amy Andreotti Alan Goldman Bruce Harmon Joerg Schmalian Iowa State University Ames, Iowa 2003 .. 11 Graduate College Iowa State University This is to certify that the doctoral dissertation of Haibo Cao has met the dissertation requirements of Iowa State University Major Professor For the Major Program ... 111 TABLE OF CONTENTS ... Acknowledgments ................................... vm Abstract and Organization of Dissertation ..................... X CHAPTER 1. Protein Structure And Building Blocks ............. 1 Proteins. .......................................... 1 AminoAcids ........................................ 3 Secondary Structure ................................... 4 aHelix ...................................... 4 psheet ......................................... 5 Bibliography ........................................ 11 CHAPTER 2 . Protein Folding Problem ...................... 13 Levinthal’s Paradox .................................... 13 Interactions ......................................... 15 MJmatrix ....................................... 16 LTW parameterization ................................ 19 Bibliography ........................................ 25 CHAPTER 3 . Simple Exact Model ....................... -
Roles of Nickel Binding Proteins in Helicobacter Species
ROLES OF NICKEL BINDING PROTEINS IN HELICOBACTER SPECIES by SUSMITHA SESHADRI (Under the Direction of Robert J. Maier) ABSTRACT Proteins Hpn and Hpn-like of the gastric pathogen H. pylori were hypothesized to bind nickel since histidine residues make up 45% and 27% of their amino acid content, respectively. Characterization of an hpn, an hpn-like and an hpn, hpn-like double mutant revealed novel functions for these gene products in nickel detoxification and storage. Compared to the wild-type parent, mutant strains were more sensitive to elevated concentrations of nickel, cobalt, and cadmium, indicating roles for the two proteins in surviving metal toxicity. Under low nickel conditions, the mutants exhibited higher urease activities and had increased amount of Ni- associated with urease; but similar urease apo-protein levels to wild-type. The parent achieved mutant level urease activities under nickel supplementation and lower pH conditions while growth with a nickel chelator decreased mutant but not wild-type urease activities. These results strongly imply a role for these proteins as nickel reservoirs/storage proteins. H. hepaticus colonizes a non-acidic niche, hence nickel metabolism may be different than in H. pylori. A nikR mutant exhibited higher urease and hydrogenase activities under all supplemental nickel conditions, but there was no change in urease expression, and NikR did not bind pUreA or pHydA. Higher total nickel levels (detected by ICP-MS) in the nikR mutant implied possible higher nickel transporter (NikA) levels, which was later verified by qRT-PCR and binding of NikR to pNikA. Periplasmic nitrate reductase (NapA) was upregulated in the NikR strain. -
A Highly Accurate Model for Screening Prostate Cancer Using Propensity Index Panel of Ten Genes
bioRxiv preprint doi: https://doi.org/10.1101/2021.03.22.436371; this version posted March 22, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. A highly accurate model for screening prostate cancer using propensity index panel of ten genes Shipra Jain#, Kawal Preet Kaur Malhotra#, Sumeet Patiyal#, Gajendra P. S. Raghava* Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi-110020, India. # - Contributed Equally * - Corresponding Author Mailing Address of Authors Shipra Jain: [email protected] ORCID ID: https://orcid.org/0000-0002-7045-5188 Kawal Preet Kaur Malhotra: [email protected] Sumeet Patiyal: [email protected] ORCID ID: https://orcid.org/0000-0003-1358-292X GPS Raghava: [email protected] ORCID ID: https://orcid.org/0000-0002-8902-2876 Corresponding Author Gajendra Pal Singh Raghava Head and Professor, Department of Computational Biology Office: A-302 R&D Block, Indraprastha Institute of Information Technology, Delhi Okhla Industrial Estate, Phase III, (Near Govind Puri Metro Station) New Delhi, India - 110020 Phone: 011-26907444 Email: [email protected] Website: http://webs.iiitd.edu.in/raghava/ Highlights ● Application of Machine learning techniques to identify Biomarkers for PRAD cancer. ● Highly accurate models developed for classifying prostate cancer vs. normal sample. ● Introducing Propensity index concept for enhancing model performance. ● Top 10 genes identified using feature selection techniques. bioRxiv preprint doi: https://doi.org/10.1101/2021.03.22.436371; this version posted March 22, 2021. -
The Human Genome Project
TO KNOW OURSELVES ❖ THE U.S. DEPARTMENT OF ENERGY AND THE HUMAN GENOME PROJECT JULY 1996 TO KNOW OURSELVES ❖ THE U.S. DEPARTMENT OF ENERGY AND THE HUMAN GENOME PROJECT JULY 1996 Contents FOREWORD . 2 THE GENOME PROJECT—WHY THE DOE? . 4 A bold but logical step INTRODUCING THE HUMAN GENOME . 6 The recipe for life Some definitions . 6 A plan of action . 8 EXPLORING THE GENOMIC LANDSCAPE . 10 Mapping the terrain Two giant steps: Chromosomes 16 and 19 . 12 Getting down to details: Sequencing the genome . 16 Shotguns and transposons . 20 How good is good enough? . 26 Sidebar: Tools of the Trade . 17 Sidebar: The Mighty Mouse . 24 BEYOND BIOLOGY . 27 Instrumentation and informatics Smaller is better—And other developments . 27 Dealing with the data . 30 ETHICAL, LEGAL, AND SOCIAL IMPLICATIONS . 32 An essential dimension of genome research Foreword T THE END OF THE ROAD in Little has been rapid, and it is now generally agreed Cottonwood Canyon, near Salt that this international project will produce Lake City, Alta is a place of the complete sequence of the human genome near-mythic renown among by the year 2005. A skiers. In time it may well And what is more important, the value assume similar status among molecular of the project also appears beyond doubt. geneticists. In December 1984, a conference Genome research is revolutionizing biology there, co-sponsored by the U.S. Department and biotechnology, and providing a vital of Energy, pondered a single question: Does thrust to the increasingly broad scope of the modern DNA research offer a way of detect- biological sciences. -
Combinatorial Algorithms for Protein Folding in Lattice Models: a Survey of Mathematical Results
Combinatorial Algorithms for Protein Folding in Lattice Models: A Survey of Mathematical Results Sorin Istrail∗ Center for Computational Molecular Biology Department of Computer Science Brown University Providence, RI 02912 Fumei Lam† Center for Computational Molecular Biology Department of Computer Science Brown University Providence, RI 02912 Dedicated to Michael Waterman’s 67th Birthday June 17, 2009 “ ... a very nice step forward in the computerology of proteins.” Ken Dill 1995[1] Abstract We present a comprehensive survey of combinatorial algorithms and theorems about lattice protein folding models obtained in the almost 15 years since the publication in 1995 of the first protein folding approximation algorithm with mathematically guar- anteed error bounds [60]. The results presented here are mainly about the HP-protein folding model introduced by Ken Dill in 1985 [37]. The main topics of this survey include: approximation algorithms for linear-chain and side-chain lattice models, as well as off-lattice models, NP-completeness theorems about a variety of protein folding models, contact map structure of self-avoiding walks and HP-folds, combinatorics and algorithmics of side-chain models, bi-sphere packing and the Kepler conjecture, and the protein side-chain self-assembly conjecture. As an appealing bridge between the hybrid of continuous mathematics and discrete mathematics, a cornerstone of the mathemat- ical difficulty of the protein folding problem, we show how work on 2D self-avoiding walks contact-map decomposition [56] can build upon the exact RNA contacts counting formula by Mike Waterman and collaborators [96] which lead to renewed hope for ana- lytical closed-form approximations for statistical mechanics of protein folding in lattice models. -
Arxiv:2004.01118V2 [Quant-Ph] 18 May 2021
Investigating the potential for a limited quantum speedup on protein lattice problems Carlos Outeiral1;2, Garrett M. Morris1, Jiye Shi3, Martin Strahm4, Simon C. Benjamin2;∗, Charlotte M. Deane1;y 1Department of Statistics, University of Oxford, 24-29 St Giles', Oxford OX1 3LB, United Kingdom 2Department of Materials, University of Oxford, Parks Road, Oxford OX1 3PH, United Kingdom 3Computer-Aided Drug Design, UCB Pharma, 216 Bath Road, Slough SL1 3WE, United Kingdom 4Pharma Research & Early Development, F. Hoffmann-La Roche, Grenzacherstrasse 4058, Basel, Switzerland ∗To whom correspondence shall be addressed: [email protected] yTo whom correspondence shall be addressed: [email protected] Abstract. Protein folding is a central challenge in computational biology, with important applications in molecular biology, drug discovery and catalyst design. As a hard combinatorial optimisation problem, it has been studied as a potential target problem for quantum annealing. Although several experimental implementations have been discussed in the literature, the computational scaling of these approaches has not been elucidated. In this article, we present a numerical study of quantum annealing applied to a large number of small peptide folding problems, aiming to infer useful insights for near-term applications. We present two conclusions: that even na¨ıve quantum annealing, when applied to protein lattice folding, has the potential to outperform classical approaches, and that careful engineering of the Hamiltonians and schedules involved can deliver notable relative improvements for this problem. Overall, our results suggest that quantum algorithms may well offer improvements for problems in the protein folding and structure prediction realm. arXiv:2004.01118v2 [quant-ph] 18 May 2021 Keywords: quantum annealing, protein folding, quantum optimisation, biophysics 1. -
Complex Rearrangement of Chromosomes 19, 21, and 22 In
Cancer Genetics and Cytogenetics 181 (2008) 81e92 Complex rearrangement of chromosomes 19, 21, and 22 in Ewing sarcoma involving a novel reciprocal inversioneinsertion mechanism of EWSeERG fusion gene formation: a case analysis and literature review Georges Mairea, Christopher W. Brownb,c,d, Jane Bayania, Carlos Pereirae, Denis H. Gravelf, John C. Bellc, Maria Zielenskae,g,h, Jeremy A. Squirea,h* aDivision of Applied Molecular Oncology, Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, 610 University Avenue, Room 9-717, Toronto, Ontario M5G 2M9, Canada bOttawa Health Research Institute, Centre for Cancer Therapeutics, Ottawa, Ontario, Canada cDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada dDepartment of Orthopaedic Surgery, Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada eDepartment of Pediatric Laboratory Medicine and Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada fDepartment of Pathology and Laboratory Medicine, Ottawa Hospital and University of Ottawa, Ottawa, Ontario, Canada gGenetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada hDepartment of Laboratory Medicine and Pathology, University of Toronto, Toronto, Ontario, Canada Received 9 August 2007; received in revised form 5 November 2007; accepted 7 November 2007 Abstract EWSeERG Ewing sarcoma (ES) gene fusions often result from complex chromosomal rearrange- ments. We report an unusually aggressive case of ES with an EWSeERG fusion gene that appeared to be a result of a simple balanced and reciprocal translocation, t(19;22)(q13.2;q12.2). Subsequent molecular investigation of the primary tumor, the metastasis, and a cell line generated from this ES permitted reconstruction of each genomic step in the evolution of this complex EWSeERG fusion. -
COMPUTATIONAL MODELLING of PROTEIN FIBRILLATION with APPLICATION to GLUCAGON Hamed Tabatabaei Ghomi Purdue University
Purdue University Purdue e-Pubs Open Access Dissertations Theses and Dissertations January 2015 COMPUTATIONAL MODELLING OF PROTEIN FIBRILLATION WITH APPLICATION TO GLUCAGON Hamed Tabatabaei Ghomi Purdue University Follow this and additional works at: https://docs.lib.purdue.edu/open_access_dissertations Recommended Citation Tabatabaei Ghomi, Hamed, "COMPUTATIONAL MODELLING OF PROTEIN FIBRILLATION WITH APPLICATION TO GLUCAGON" (2015). Open Access Dissertations. 1321. https://docs.lib.purdue.edu/open_access_dissertations/1321 This document has been made available through Purdue e-Pubs, a service of the Purdue University Libraries. Please contact [email protected] for additional information. i COMPUTATIONAL MODELLING OF PROTEIN FIBRILLATION WITH APPLICATION TO GLUCAGON A Dissertation Submitted to the Faculty of Purdue University by Hamed Tabatabaei Ghomi In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy i December 2015 Purdue University West Lafayette, Indiana ii ای الهه ای رتاهن ام آشیاهن ام یس ای ربای شاد ز تن بهاهن ام قهرمان قصه اهی عاشقاهن ام نس با یم انم تو بهار می شود بذر شعراهی اتزه رد میان خاک بی رقار می شود ii iii ACKNOWLEDGEMENTS I am indebted to my advisors, Dr. Lill and Dr. Topp who taught me many things about science, and about life. Also, I thank my advisory committee, Dr. Park, Dr. Post and Dr. Kihara for all their support. I am grateful to my lovely wife, Elaheh. I owe all my success to her support and sacrifice. I am also grateful to my parent for their support and encouragement. And finally, I owe my deepest and greatest gratitude to God, the Most Beneficent, the Most Merciful. -
S41419-021-03972-6.Pdf
www.nature.com/cddis ARTICLE OPEN Primed to die: an investigation of the genetic mechanisms underlying noise-induced hearing loss and cochlear damage in homozygous Foxo3-knockout mice ✉ Holly J. Beaulac1,3, Felicia Gilels1,4, Jingyuan Zhang1,5, Sarah Jeoung2 and Patricia M. White 1 © The Author(s) 2021 The prevalence of noise-induced hearing loss (NIHL) continues to increase, with limited therapies available for individuals with cochlear damage. We have previously established that the transcription factor FOXO3 is necessary to preserve outer hair cells (OHCs) and hearing thresholds up to two weeks following mild noise exposure in mice. The mechanisms by which FOXO3 preserves cochlear cells and function are unknown. In this study, we analyzed the immediate effects of mild noise exposure on wild-type, Foxo3 heterozygous (Foxo3+/−), and Foxo3 knock-out (Foxo3−/−) mice to better understand FOXO3’s role(s) in the mammalian cochlea. We used confocal and multiphoton microscopy to examine well-characterized components of noise-induced damage including calcium regulators, oxidative stress, necrosis, and caspase-dependent and caspase-independent apoptosis. Lower immunoreactivity of the calcium buffer Oncomodulin in Foxo3−/− OHCs correlated with cell loss beginning 4 h post-noise exposure. Using immunohistochemistry, we identified parthanatos as the cell death pathway for OHCs. Oxidative stress response pathways were not significantly altered in FOXO3’s absence. We used RNA sequencing to identify and RT-qPCR to confirm differentially expressed genes. We further investigated a gene downregulated in the unexposed Foxo3−/− mice that may contribute to OHC noise susceptibility. Glycerophosphodiester phosphodiesterase domain containing 3 (GDPD3), a possible endogenous source of lysophosphatidic acid (LPA), has not previously been described in the cochlea.