Structural Bioinformatics
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An Effective Computational Method Incorporating Multiple Secondary
Old Dominion University ODU Digital Commons Computer Science Faculty Publications Computer Science 2017 An Effective Computational Method Incorporating Multiple Secondary Structure Predictions in Topology Determination for Cryo-EM Images Abhishek Biswas Old Dominion University Desh Ranjan Old Dominion University Mohammad Zubair Old Dominion University Stephanie Zeil Old Dominion University Kamal Al Nasr See next page for additional authors Follow this and additional works at: https://digitalcommons.odu.edu/computerscience_fac_pubs Part of the Biochemistry Commons, Computer Sciences Commons, Molecular Biology Commons, and the Statistics and Probability Commons Repository Citation Biswas, Abhishek; Ranjan, Desh; Zubair, Mohammad; Zeil, Stephanie; Al Nasr, Kamal; and He, Jing, "An Effective Computational Method Incorporating Multiple Secondary Structure Predictions in Topology Determination for Cryo-EM Images" (2017). Computer Science Faculty Publications. 81. https://digitalcommons.odu.edu/computerscience_fac_pubs/81 Original Publication Citation Biswas, A., Ranjan, D., Zubair, M., Zeil, S., Al Nasr, K., & He, J. (2017). An effective computational method incorporating multiple secondary structure predictions in topology determination for cryo-em images. IEEE/ACM Transactions on Computational Biology and Bioinformatics, 14(3), 578-586. doi:10.1109/tcbb.2016.2543721 This Article is brought to you for free and open access by the Computer Science at ODU Digital Commons. It has been accepted for inclusion in Computer Science Faculty Publications by an authorized administrator of ODU Digital Commons. For more information, please contact [email protected]. Authors Abhishek Biswas, Desh Ranjan, Mohammad Zubair, Stephanie Zeil, Kamal Al Nasr, and Jing He This article is available at ODU Digital Commons: https://digitalcommons.odu.edu/computerscience_fac_pubs/81 HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author IEEE/ACM Manuscript Author Trans Comput Manuscript Author Biol Bioinform. -
Protein Structure: Data Bases and Classification
Protein Structure: Data Bases and Classification Ingo Ruczinski Department of Biostatistics, Johns Hopkins University Reference Bourne and Weissig Structural Bioinformatics Wiley, 2003 More References 1 Structural Proteins Membrane Proteins Globular Proteins 2 Terminology • Primary Structure • Secondary Structure • Tertiary Structure • Quatenary Structure • Supersecondary Structure • Domain • Fold Hierarchy of Protein Structure Helices α 3.10 π Amino acids/turn: 3.6 3.0 4.4 Frequency ~97% ~3% rare H-bonding i, i+4 i, i+3 i, i+5 3 α-helices α-helices α-helices have handedness: α-helices have a dipole: β-sheets 4 β-sheets Have a right-handed twist! β-sheets Can form higher level structures! Super Secondary Structure Motifs 5 What is a Domain? Richardson (1981): W ithin a single subunit [polypeptide chain], contiguous portions of the polypeptide chain frequently fold into compact, local semi-independent units called domains. More About Domains • Independent folding units. • Lots of within contacts, few outside. • Domains create their own hydrophobic core. • Regions usually conserved during recombination. • Different domains of the same protein can have different functions. • Domains of the same protein may or may not interact. Why Look for Domains? Domains are the currency of protein function! 6 Domain Size • Domains can be between 25 and 500 residues long. • Most are less than 200 residues. • Domains can be smaller than 50 residues, but these need to be stabilized. Examples are the zinc finger and a scorpion toxin. Two Very Small Domains A Humdinger of a Domain 7 What’s the Domain? (Part 1) What’s the Domain? (Part 2) Homology and Analogy • Homology: Similarity in characteristics resulting from shared ancestry. -
A Community Proposal to Integrate Structural
F1000Research 2020, 9(ELIXIR):278 Last updated: 11 JUN 2020 OPINION ARTICLE A community proposal to integrate structural bioinformatics activities in ELIXIR (3D-Bioinfo Community) [version 1; peer review: 1 approved, 3 approved with reservations] Christine Orengo1, Sameer Velankar2, Shoshana Wodak3, Vincent Zoete4, Alexandre M.J.J. Bonvin 5, Arne Elofsson 6, K. Anton Feenstra 7, Dietland L. Gerloff8, Thomas Hamelryck9, John M. Hancock 10, Manuela Helmer-Citterich11, Adam Hospital12, Modesto Orozco12, Anastassis Perrakis 13, Matthias Rarey14, Claudio Soares15, Joel L. Sussman16, Janet M. Thornton17, Pierre Tuffery 18, Gabor Tusnady19, Rikkert Wierenga20, Tiina Salminen21, Bohdan Schneider 22 1Structural and Molecular Biology Department, University College, London, UK 2Protein Data Bank in Europe, European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, CB10 1SD, UK 3VIB-VUB Center for Structural Biology, Brussels, Belgium 4Department of Oncology, Lausanne University, Swiss Institute of Bioinformatics, Lausanne, Switzerland 5Bijvoet Center, Faculty of Science – Chemistry, Utrecht University, Utrecht, 3584CH, The Netherlands 6Science for Life Laboratory, Stockholm University, Solna, S-17121, Sweden 7Dept. Computer Science, Center for Integrative Bioinformatics VU (IBIVU), Vrije Universiteit, Amsterdam, 1081 HV, The Netherlands 8Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, L-4367, Luxembourg 9Bioinformatics center, Department of Biology, University of Copenhagen, Copenhagen, DK-2200, -
Chapter 13 Protein Structure Learning Objectives
Chapter 13 Protein structure Learning objectives Upon completing this material you should be able to: ■ understand the principles of protein primary, secondary, tertiary, and quaternary structure; ■use the NCBI tool CN3D to view a protein structure; ■use the NCBI tool VAST to align two structures; ■explain the role of PDB including its purpose, contents, and tools; ■explain the role of structure annotation databases such as SCOP and CATH; and ■describe approaches to modeling the three-dimensional structure of proteins. Outline Overview of protein structure Principles of protein structure Protein Data Bank Protein structure prediction Intrinsically disordered proteins Protein structure and disease Overview: protein structure The three-dimensional structure of a protein determines its capacity to function. Christian Anfinsen and others denatured ribonuclease, observed rapid refolding, and demonstrated that the primary amino acid sequence determines its three-dimensional structure. We can study protein structure to understand problems such as the consequence of disease-causing mutations; the properties of ligand-binding sites; and the functions of homologs. Outline Overview of protein structure Principles of protein structure Protein Data Bank Protein structure prediction Intrinsically disordered proteins Protein structure and disease Protein primary and secondary structure Results from three secondary structure programs are shown, with their consensus. h: alpha helix; c: random coil; e: extended strand Protein tertiary and quaternary structure Quarternary structure: the four subunits of hemoglobin are shown (with an α 2β2 composition and one beta globin chain high- lighted) as well as four noncovalently attached heme groups. The peptide bond; phi and psi angles The peptide bond; phi and psi angles in DeepView Protein secondary structure Protein secondary structure is determined by the amino acid side chains. -
Characterization of TSET, an Ancient and Widespread Membrane
RESEARCH ARTICLE elifesciences.org Characterization of TSET, an ancient and widespread membrane trafficking complex Jennifer Hirst1*†, Alexander Schlacht2†, John P Norcott3‡, David Traynor4‡, Gareth Bloomfield4, Robin Antrobus1, Robert R Kay4, Joel B Dacks2*, Margaret S Robinson1* 1Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; 2Department of Cell Biology, University of Alberta, Edmonton, Canada; 3Department of Engineering, University of Cambridge, Cambridge, United Kingdom; 4Cell Biology, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom Abstract The heterotetrameric AP and F-COPI complexes help to define the cellular map of modern eukaryotes. To search for related machinery, we developed a structure-based bioinformatics tool, and identified the core subunits of TSET, a 'missing link' between the APs and COPI. Studies in Dictyostelium indicate that TSET is a heterohexamer, with two associated scaffolding proteins. TSET is non-essential in Dictyostelium, but may act in plasma membrane turnover, and is essentially identical to the recently described TPLATE complex, TPC. However, whereas TPC was reported to be plant-specific, we can identify a full or partial complex in every *For correspondence: jh228@ eukaryotic supergroup. An evolutionary path can be deduced from the earliest origins of the cam.ac.uk (JH); [email protected] (JBD); [email protected] (MSR) heterotetramer/scaffold coat to its multiple manifestations in modern organisms, including the mammalian muniscins, descendants of the TSET medium subunits. Thus, we have uncovered † These authors contributed the machinery for an ancient and widespread pathway, which provides new insights into early equally to this work eukaryotic evolution. ‡These authors also contributed DOI: 10.7554/eLife.02866.001 equally to this work Competing interests: The authors declare that no competing interests exist. -
Increasing the Accuracy of Single Sequence Prediction Methods Using a Deep Semi-Supervised Learning Framework Lewis Moffat 1,∗ and David T
Structural Bioinformatics Downloaded from https://academic.oup.com/bioinformatics/advance-article/doi/10.1093/bioinformatics/btab491/6313164 by guest on 07 July 2021 Increasing the Accuracy of Single Sequence Prediction Methods Using a Deep Semi-Supervised Learning Framework Lewis Moffat 1,∗ and David T. Jones 1,∗ 1Department of Computer Science, University College London, Gower Street, London WC1E 6BT, UK; and Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK ∗To whom correspondence should be addressed. Associate Editor: XXXXXXX Received on XXXXX; revised on XXXXX; accepted on XXXXX Abstract Motivation: Over the past 50 years, our ability to model protein sequences with evolutionary information has progressed in leaps and bounds. However, even with the latest deep learning methods, the modelling of a critically important class of proteins, single orphan sequences, remains unsolved. Results: By taking a bioinformatics approach to semi-supervised machine learning, we develop Profile Augmentation of Single Sequences (PASS), a simple but powerful framework for building accurate single- sequence methods. To demonstrate the effectiveness of PASS we apply it to the mature field of secondary structure prediction. In doing so we develop S4PRED, the successor to the open-source PSIPRED-Single method, which achieves an unprecedented Q3 score of 75.3% on the standard CB513 test. PASS provides a blueprint for the development of a new generation of predictive methods, advancing our ability to model individual protein sequences. Availability: The S4PRED model is available as open source software on the PSIPRED GitHub repository (https://github.com/psipred/s4pred), along with documentation. It will also be provided as a part of the PSIPRED web service (http://bioinf.cs.ucl.ac.uk/psipred/) Contact: [email protected], [email protected] Supplementary information: Supplementary data are available at Bioinformatics online. -
Water in Protein Structure Prediction
Water in protein structure prediction Garegin A. Papoian†‡, Johan Ulander†‡§, Michael P. Eastwood†¶, Zaida Luthey-Schultenʈ, and Peter G. Wolynes†,†† †Department of Chemistry and Biochemistry and Center for Theoretical Biological Physics, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0371; and ʈDepartment of Chemistry, University of Illinois at Urbana–Champaign, Urbana, IL 61801 Contributed by Peter G. Wolynes, December 4, 2003 Proteins have evolved to use water to help guide folding. A interactions play an important role not only in binding interfaces physically motivated, nonpairwise-additive model of water-medi- but in folding of monomeric proteins. ated interactions added to a protein structure prediction Hamilto- We use the associative memory (AM) Hamiltonian molecular nian yields marked improvement in the quality of structure pre- dynamics model as a starting point (14–16). This Hamiltonian diction for larger proteins. Free energy profile analysis suggests has two principal components: general polymer physics-based that long-range water-mediated potentials guide folding and terms that are sequence independent, collectively called ‘‘back- smooth the underlying folding funnel. Analyzing simulation tra- bone,’’ and sequence-dependent knowledge-based distance- jectories gives direct evidence that water-mediated interactions dependent additive potentials, collectively denoted as AM͞C facilitate native-like packing of supersecondary structural ele- (AM͞contact). The AM part describes interactions between all ments. Long-range pairing of hydrophilic groups is an integral part pairs of residues that are separated in sequence between 3 and of protein architecture. Specific water-mediated interactions are a 12 residues. It uses a set of nonhomologous memory proteins to universal feature of biomolecular recognition landscapes in both build a funneled energy landscape by matching fragments. -
Structure Prediction, Fold Recognition and Homology Modelling
Structure prediction, fold recognition and homology modelling Marjolein Thunnissen Lund September 2009 Steps in protein modelling Similarity search (BLAST) Multiple alignment 3-D structure known No Structure known Comparative Modelling Secondary structure prediction Fold recognition Ab initio (Rosetta) Structure Prediction 1) Prediction of secondary structure. a) Method of Chou and Fasman b) Neural networks c) hydrophobicity plots 2) Prediction of tertiary structure. a) Ab initio structure prediction b) Threading - 1D-3D profiles - Knowledge based potentials c) Homology modelling How does sequence identity correlate with structural similarity Analysis by Chotia and Lesk (89) • 100% sequence identity: rmsd = experimental error • <25% (twilight zone), structures might be similar but can also be different • Rigid body movements make rmsd bigger Secondary structure prediction: Take the sequence and, using rules derived from known structures, predict the secondary structure that is most likely to be adopted by each residue Why secondary structure prediction ? • A major part of the general folding prediction problem. • The first method of obtaining some structural information from a newly determined sequence. Rules governing !-helix and "-sheet structures provide guidelines for selecting specific mutations. • Assignment of sec. str. can help to confirm structural and functional relationship between proteins when sequences homology is weak (used in threading experiments). • Important in establishing alignments during model building by homology; the first step in attempts to generate 3D models Some interesting facts 2nd structure predictions • based on primary sequence only • accuracy 64% -75% • higher accuracy for !-helices than "! strands • accuracy is dependent on protein family • predictions of engineered proteins are less accurate Methods: •Statistical methods based on studies of databases of known protein structures from which structural propensities for all amino acids are calculated. -
Bi-Allelic Novel Variants in CLIC5 Identified in a Cameroonian
G C A T T A C G G C A T genes Article Bi-Allelic Novel Variants in CLIC5 Identified in a Cameroonian Multiplex Family with Non-Syndromic Hearing Impairment Edmond Wonkam-Tingang 1, Isabelle Schrauwen 2 , Kevin K. Esoh 1 , Thashi Bharadwaj 2, Liz M. Nouel-Saied 2 , Anushree Acharya 2, Abdul Nasir 3 , Samuel M. Adadey 1,4 , Shaheen Mowla 5 , Suzanne M. Leal 2 and Ambroise Wonkam 1,* 1 Division of Human Genetics, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa; [email protected] (E.W.-T.); [email protected] (K.K.E.); [email protected] (S.M.A.) 2 Center for Statistical Genetics, Sergievsky Center, Taub Institute for Alzheimer’s Disease and the Aging Brain, and the Department of Neurology, Columbia University Medical Centre, New York, NY 10032, USA; [email protected] (I.S.); [email protected] (T.B.); [email protected] (L.M.N.-S.); [email protected] (A.A.); [email protected] (S.M.L.) 3 Synthetic Protein Engineering Lab (SPEL), Department of Molecular Science and Technology, Ajou University, Suwon 443-749, Korea; [email protected] 4 West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, Accra LG 54, Ghana 5 Division of Haematology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa; [email protected] * Correspondence: [email protected]; Tel.: +27-21-4066-307 Received: 28 September 2020; Accepted: 20 October 2020; Published: 23 October 2020 Abstract: DNA samples from five members of a multiplex non-consanguineous Cameroonian family, segregating prelingual and progressive autosomal recessive non-syndromic sensorineural hearing impairment, underwent whole exome sequencing. -
Further Confirmation of the Association of SLC12A2 with Non-Syndromic
www.nature.com/jhg ARTICLE OPEN Further confirmation of the association of SLC12A2 with non-syndromic autosomal-dominant hearing impairment Samuel M. Adadey1,2,9, Isabelle Schrauwen3,9, Elvis Twumasi Aboagye1, Thashi Bharadwaj3, Kevin K. Esoh 2, Sulman Basit 4, 3 3 5 2 6 1 Anushree Acharya , Liz M. Nouel-Saied ,✉ Khurram Liaqat , Edmond✉ Wonkam-Tingang , Shaheen Mowla , Gordon A. Awandare , Wasim Ahmad 7, Suzanne M. Leal 3,8 and Ambroise Wonkam 2 © The Author(s) 2021 Congenital hearing impairment (HI) is genetically heterogeneous making its genetic diagnosis challenging. Investigation of novel HI genes and variants will enhance our understanding of the molecular mechanisms and to aid genetic diagnosis. We performed exome sequencing and analysis using DNA samples from affected members of two large families from Ghana and Pakistan, segregating autosomal-dominant (AD) non-syndromic HI (NSHI). Using in silico approaches, we modeled and evaluated the effect of the likely pathogenic variants on protein structure and function. We identified two likely pathogenic variants in SLC12A2, c.2935G>A:p.(E979K) and c.2939A>T:p.(E980V), which segregate with NSHI in a Ghanaian and Pakistani family, respectively. SLC12A2 encodes an ion transporter crucial in the homeostasis of the inner ear endolymph and has recently been reported to be implicated in syndromic and non-syndromic HI. Both variants were mapped to alternatively spliced exon 21 of the SLC12A2 gene. Exon 21 encodes for 17 residues in the cytoplasmatic tail of SLC12A2, is highly conserved between species, and preferentially expressed in cochlear tissues. A review of previous studies and our current data showed that out of ten families with either AD non-syndromic or syndromic HI, eight (80%) had variants within the 17 amino acid residue region of exon 21 (48 bp), suggesting that this alternate domain is critical to the transporter activity in the inner ear. -
Bayesian Model of Protein Primary Sequence for Secondary Structure Prediction
Bayesian Model of Protein Primary Sequence for Secondary Structure Prediction Qiwei Li1, David B. Dahl2*, Marina Vannucci1, Hyun Joo3, Jerry W. Tsai3 1 Department of Statistics, Rice University, Houston, Texas, United States of America, 2 Department of Statistics, Brigham Young University, Provo, Utah, United States of America, 3 Department of Chemistry, University of the Pacific, Stockton, California, United States of America Abstract Determining the primary structure (i.e., amino acid sequence) of a protein has become cheaper, faster, and more accurate. Higher order protein structure provides insight into a protein’s function in the cell. Understanding a protein’s secondary structure is a first step towards this goal. Therefore, a number of computational prediction methods have been developed to predict secondary structure from just the primary amino acid sequence. The most successful methods use machine learning approaches that are quite accurate, but do not directly incorporate structural information. As a step towards improving secondary structure reduction given the primary structure, we propose a Bayesian model based on the knob- socket model of protein packing in secondary structure. The method considers the packing influence of residues on the secondary structure determination, including those packed close in space but distant in sequence. By performing an assessment of our method on 2 test sets we show how incorporation of multiple sequence alignment data, similarly to PSIPRED, provides balance and improves the accuracy of the predictions. Software implementing the methods is provided as a web application and a stand-alone implementation. Citation: Li Q, Dahl DB, Vannucci M, Joo H, Tsai JW (2014) Bayesian Model of Protein Primary Sequence for Secondary Structure Prediction. -
The Structure and Dynamics of Bmr1 Protein from Brugia Malayi: in Silico Approaches
Int. J. Mol. Sci. 2014, 15, 11082-11099; doi:10.3390/ijms150611082 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms Article The Structure and Dynamics of BmR1 Protein from Brugia malayi: In Silico Approaches Bee Yin Khor, Gee Jun Tye, Theam Soon Lim, Rahmah Noordin and Yee Siew Choong * Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, Penang 11800, Malaysia; E-Mails: [email protected] (B.Y.K.); [email protected] (G.J.T.); [email protected] (T.S.L.); [email protected] (R.N.) * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +604-653-4837; Fax: +604-653-4803. Received: 28 January 2014; in revised form: 25 March 2014 / Accepted: 4 June 2014 / Published: 19 June 2014 Abstract: Brugia malayi is a filarial nematode, which causes lymphatic filariasis in humans. In 1995, the disease has been identified by the World Health Organization (WHO) as one of the second leading causes of permanent and long-term disability and thus it is targeted for elimination by year 2020. Therefore, accurate filariasis diagnosis is important for management and elimination programs. A recombinant antigen (BmR1) from the Bm17DIII gene product was used for antibody-based filariasis diagnosis in “Brugia Rapid”. However, the structure and dynamics of BmR1 protein is yet to be elucidated. Here we study the three dimensional structure and dynamics of BmR1 protein using comparative modeling, threading and ab initio protein structure prediction. The best predicted structure obtained via an ab initio method (Rosetta) was further refined and minimized.