Ribbon Diagrams and Protein Taxonomy: Shirley Chan a Profile of Jane S
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MATHEMATICAL TECHNIQUES in STRUCTURAL BIOLOGY Contents 0. Introduction 4 1. Molecular Genetics: DNA 6 1.1. Genetic Code 6 1.2. T
MATHEMATICAL TECHNIQUES IN STRUCTURAL BIOLOGY J. R. QUINE Contents 0. Introduction 4 1. Molecular Genetics: DNA 6 1.1. Genetic code 6 1.2. The geometry of DNA 6 1.3. The double helix 6 1.4. Larger organization of DNA 7 1.5. DNA and proteins 7 1.6. Problems 7 2. Molecular Genetics: Proteins 10 2.1. Amino Acids 10 2.2. The genetic code 10 2.3. Amino acid template 11 2.4. Tetrahedral geometry 11 2.5. Amino acid structure 13 2.6. The peptide bond 13 2.7. Protein structure 14 2.8. Secondary structure 14 3. Frames and moving frames 19 3.1. Basic definitions 19 3.2. Frames and gram matrices 19 3.3. Frames and rotations 20 3.4. Frames fixed at a point 20 3.5. The Frenet Frame 20 3.6. The coiled-coil 22 3.7. The Frenet formula 22 3.8. Problems 24 4. Orthogonal transformations and Rotations 25 4.1. The rotation group 25 4.2. Complex form of a rotation 28 4.3. Eigenvalues of a rotation 28 4.4. Properties of rotations 29 4.5. Problems 30 5. Torsion angles and pdb files 33 5.1. Torsion Angles 33 5.2. The arg function 34 5.3. The torsion angle formula 34 5.4. Protein torsion angles. 35 5.5. Protein Data Bank files. 35 1 2 J. R. QUINE 5.6. Ramachandran diagram 36 5.7. Torsion angles on the diamond packing 37 5.8. Appendix, properties of cross product 38 5.9. Problems 38 6. -
Conformational Transition of H-Shaped Branched Polymers
1 Conformational Transition of H-shaped Branched Polymers Ashok Kumar Dasmahapatra* and Venkata Mahanth Sanka Department of Chemical Engineering, Indian Institute of Technology Guwahati, Guwahati – 781039, Assam, India PACS number(s): 83.80.Rs, 87.10.Rt, 82.20.Wt, 61.25.he * Corresponding author: Phone: +91-361-258-2273; Fax: +91-361-258-2291; Email address: [email protected] 2 ABSTRACT We report dynamic Monte Carlo simulation on conformational transition of H-shaped branched polymers by varying main chain (backbone) and side chain (branch) length. H- shaped polymers in comparison with equivalent linear polymers exhibit a depression of theta temperature accompanying with smaller chain dimensions. We observed that the effect of branches on backbone dimension is more pronounced than the reverse, and is attributed to the conformational heterogeneity prevails within the molecule. With increase in branch length, backbone is slightly stretched out in coil and globule state. However, in the pre-collapsed (cf. crumpled globule) state, backbone size decreases with the increase of branch length. We attribute this non-monotonic behavior as the interplay between excluded volume interaction and intra-chain bead-bead attractive interaction during collapse transition. Structural analysis reveals that the inherent conformational heterogeneity promotes the formation of a collapsed structure with segregated backbone and branch units (resembles to “sandwich” or “Janus” morphology) rather an evenly distributed structure comprising of all the units. The shape of the collapsed globule becomes more spherical with increasing either backbone or branch length. 3 I. INTRODUCTION Branched polymers are commodious in preparing tailor-made materials for various applications such as in the area of catalysis1, nanomaterials2, and biomedicines3. -
Electrically Sensing Hachimoji DNA Nucleotides Through a Hybrid Graphene/H-BN Nanopore Cite This: Nanoscale, 2020, 12, 18289 Fábio A
Nanoscale View Article Online PAPER View Journal | View Issue Electrically sensing Hachimoji DNA nucleotides through a hybrid graphene/h-BN nanopore Cite this: Nanoscale, 2020, 12, 18289 Fábio A. L. de Souza, †a Ganesh Sivaraman, †b,g Maria Fyta, †c Ralph H. Scheicher, *†d Wanderlã L. Scopel †e and Rodrigo G. Amorim *†f The feasibility of synthesizing unnatural DNA/RNA has recently been demonstrated, giving rise to new perspectives and challenges in the emerging field of synthetic biology, DNA data storage, and even the search for extraterrestrial life in the universe. In line with this outstanding potential, solid-state nanopores have been extensively explored as promising candidates to pave the way for the next generation of label- free, fast, and low-cost DNA sequencing. In this work, we explore the sensitivity and selectivity of a gra- phene/h-BN based nanopore architecture towards detection and distinction of synthetic Hachimoji nucleobases. The study is based on a combination of density functional theory and the non-equilibrium Green’s function formalism. Our findings show that the artificial nucleobases are weakly binding to the Creative Commons Attribution 3.0 Unported Licence. device, indicating a short residence time in the nanopore during translocation. Significant changes in the Received 9th June 2020, electron transmission properties of the device are noted depending on which artificial nucleobase resides Accepted 7th August 2020 in the nanopore, leading to a sensitivity in distinction of up to 80%. Our results thus indicate that the pro- DOI: 10.1039/d0nr04363j posed nanopore device setup can qualitatively discriminate synthetic nucleobases, thereby opening up rsc.li/nanoscale the feasibility of sequencing even unnatural DNA/RNA. -
The New Architectonics: an Invitation to Structural Biology
THE ANATOMICAL RECORD (NEW ANAT.) 261:198–216, 2000 FEATURE ARTICLE The New Architectonics: An Invitation To Structural Biology CLARENCE E. SCHUTT* AND UNO LINDBERG The philosophy of art might offer an epistemological basis for talking about the complexity of biological molecules in a meaningful way. The analysis of artistic compositions requires the resolution of intrinsic tensions between disparate sensory categories—color, line and form—not unlike those encountered in looking at the surfaces of protein molecules, where charge, polarity, hydrophobicity, and shape compete for our attentions. Complex living systems exhibit behaviors such as contraction waves moving along muscle fibers, or shivers passing through the growth cones of migrating neurons, that are easy to describe with common words, but difficult to explain in terms of the language of chemistry. The problem follows from a lack of everyday experience with processes that move towards equilibrium by switching between crystalline order and chain-like disorder, a commonplace occurrence in the submicroscopic world of proteins. Since most of what is understood about protein function comes from studies of isolated macromolecules in solution, a serious gap exists between what we know and what we would like to know about organized biological systems. Closing this gap can be achieved by recognizing that protein molecules reside in gradients of Gibbs free energy, where local forces and movements can be large compared with Brownian motion. Architectonics, a term borrowed from the philosophical literature, symbolizes the eventual union of the structure of theories—how our minds construct the world—with the theory of structures—or how stability is maintained in the chaotic world of microsystems. -
De Novo Nucleic Acids: a Review of Synthetic Alternatives to DNA and RNA That Could Act As † Bio-Information Storage Molecules
life Review De Novo Nucleic Acids: A Review of Synthetic Alternatives to DNA and RNA That Could Act as y Bio-Information Storage Molecules Kevin G Devine 1 and Sohan Jheeta 2,* 1 School of Human Sciences, London Metropolitan University, 166-220 Holloway Rd, London N7 8BD, UK; [email protected] 2 Network of Researchers on the Chemical Evolution of Life (NoR CEL), Leeds LS7 3RB, UK * Correspondence: [email protected] This paper is dedicated to Professor Colin B Reese, Daniell Professor of Chemistry, Kings College London, y on the occasion of his 90th Birthday. Received: 17 November 2020; Accepted: 9 December 2020; Published: 11 December 2020 Abstract: Modern terran life uses several essential biopolymers like nucleic acids, proteins and polysaccharides. The nucleic acids, DNA and RNA are arguably life’s most important, acting as the stores and translators of genetic information contained in their base sequences, which ultimately manifest themselves in the amino acid sequences of proteins. But just what is it about their structures; an aromatic heterocyclic base appended to a (five-atom ring) sugar-phosphate backbone that enables them to carry out these functions with such high fidelity? In the past three decades, leading chemists have created in their laboratories synthetic analogues of nucleic acids which differ from their natural counterparts in three key areas as follows: (a) replacement of the phosphate moiety with an uncharged analogue, (b) replacement of the pentose sugars ribose and deoxyribose with alternative acyclic, pentose and hexose derivatives and, finally, (c) replacement of the two heterocyclic base pairs adenine/thymine and guanine/cytosine with non-standard analogues that obey the Watson–Crick pairing rules. -
Chain Structure Characterization
CHAIN STRUCTURE CHARACTERIZATION Gregory Beaucage and Amit S. Kulkarni Department of Chemical and Materials Engineering, University of Cincinnati, Cincinnati, Ohio 45221-0012 I. Introduction to Structure in Synthetic Macromolecules a) Dimensionality and Statistical Descriptions b) Chain Persistence and the Kuhn Unit c) Coil Structure and Chain Scaling Transitions d) Measures of Coil Size Rg and Rh II. Local Structure and its Ramifications a) Tacticity c) Branching d) Crystallization e) Hyperbranched Polymers III. Summary 1 I. Introduction to Structure in Synthetic Macromolecules a) Dimensionality and Statistical Descriptions Synthetic polymers display some physical characteristics that we can identify as native to this class of materials, particularly shear thinning rheology, rubber elasticity, and chain folded crystals. These properties are inherent to long-chain linear and weakly branched molecules and are not drastically different across a wide range of chemical make-ups. We can consider these features to define synthetic macromolecules as a distinct category of materials. The realization of this special category of materials necessitated the definition of a structural model broad enough to encompass nylon to polyethylene yet specific enough that detailed analytically available features could be used to define the major properties of interest, especially those native to this class of materials. This structural model for polymer chains is based on the random walk statistics observed by Robert Brown in studies of pollen grains and explained by Einstein in 1905. It is a trivial exercise to construct a random walk on a cubic lattice using a PC, Figure 1. From such a walk we can observe certain features of the general model for a polymer chain. -
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bioRxiv preprint doi: https://doi.org/10.1101/201152; this version posted October 10, 2017. 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-NC 4.0 International license. Touching proteins with virtual bare hands: how to visualize protein-drug complexes and their dynamics in virtual reality Erick Martins Ratamero,1 Dom Bellini,2 Christopher G. Dowson,2 and Rudolf A. R¨omer1, ∗ 1Department of Physics, University of Warwick, Coventry, CV4 7AL, UK 2School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK (Dated: Revision : 1:0, compiled October 10, 2017) Abstract The ability to precisely visualize the atomic geometry of the interactions between a drug and its protein target in structural models is critical in predicting the correct modifications in previously identified inhibitors to create more effective next generation drugs. It is currently common practice among medicinal chemists while attempting the above to access the information contained in three-dimensional structures by using two-dimensional projections, which can preclude disclosure of useful features. A more precise visualization of the three-dimensional configuration of the atomic geometry in the models can be achieved through the implementation of immersive virtual reality (VR). In this work, we present a freely available software pipeline for visualising protein structures through VR. New customer hardware, such as the HTC Vive and the Oculus Rift utilized in this study, are available at reasonable prices. Moreover, we have combined VR visualization with fast algorithms for simulating intramolecular motions of protein flexibility, in an effort to further improve structure-lead drug design by exposing molecular interactions that might be hidden in the less informative static models. -
Why Does TNA Cross-Pair More Strongly with RNA Than with DNA? an Answer from X-Ray Analysis**
Angewandte Chemie Nucleic Acids Why Does TNA Cross-Pair More Strongly with RNA Than with DNA? An Answer From X-ray Analysis** Pradeep S. Pallan, Christopher J. Wilds, Zdzislaw Wawrzak, Ramanarayanan Krishnamurthy, Albert Eschenmoser, and Martin Egli* Scheme 1. Configuration, atom numbering, and backbone torsion angle definition in a) TNA and b) DNA. Research directed toward a chemical etiology of nucleic acid structure has recently established that l-a-threofuranosyl (3’!2’) nucleic acid (TNA) is an efficient Watson–Crickbase- TNA ligands.[4] Nitrogenous analogues of TNA in which pairing system capable of informational cross-pairing with either O3’ or O2’ is substituted by an NH group are equally both RNA and DNA.[1–3] TNA is constitutionally the simplest efficient Watson–Crickbase-pairing systems; they also cross- oligonucleotide-type nucleic acid system found so far that pair with TNA, RNA, and DNA.[5] It was recently shown that possesses this capability. Its cross-pairing with RNA is certain DNA polymerases are able to copy a TNA template stronger than with DNA.[1, 2] The backbone of TNA is shorter sequence, albeit of limited length and at a slower rate than than that of DNA and RNA since the sugar moiety in TNA with a DNA template.[6] Moreover, a DNA polymerase has contains only four carbon atoms and the phosphodiester been identified that is capable of significant TNA synthesis.[7] groups are attached to the 2’- and 3’-positions of the The combination of a DNA-dependent TNA polymerase and threofuranose ring, as opposed to the 3’- and 5’-positions as a TNA-directed DNA polymerase may enable in vitro in DNA and RNA (Scheme 1). -
Greek) Key to Structures Review of Neural Adhesion Molecules
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Neuron, Vol. 16, 261±273, February, 1996, Copyright 1996 by Cell Press The (Greek) Key to Structures Review of Neural Adhesion Molecules Daniel E. Vaughn* and Pamela J. Bjorkman*² 1988; Yoshihara et al., 1991). Many neural CAM Ig super- *Division of Biology family members include Fn-III domains arranged in tan- ² Howard Hughes Medical Institute dem with Ig-like domains (Figure 1). Three-dimensional California Institute of Technology structures are available for domains of several classes Pasadena, California 91125 of Ig-like domains and for Fn-III domains; thus, one can mentally (or using computer graphics; e.g., see Figure 4) piece together the likely structures of the extracellular Cells need to adhere specifically to cellular and extracel- regions of many neural CAMs. Cadherins are also impor- lular components of their environment to carry out di- tant neural CAMs, forming homophilic adhesion inter- verse physiological functions. Examples of such func- faces in the presence of calcium (Geiger and Ayalon, tions within the nervous system include neurite 1992). Two recent structures of cadherin domains pro- extension, synapse formation, and the myelination of vide a clue about how the adhesive interface is formed. axons. The ability to recognize multiple environmental The classification of Ig-like domains has evolved since cues and to undergo specific adhesion is critical to each the first description of the Ig superfamily (Williams and of these complex cellular functions. Recognition and Barclay, 1988) because of many recent structure deter- adhesion are mediated by cell adhesion molecules minations. -
Bottlebrush Polymers in the Melt and Polyelectrolytes in Solution Share Common Structural Features
Bottlebrush polymers in the melt and polyelectrolytes in solution share common structural features Joel M. Sarapasa, Tyler B. Martina, Alexandros Chremosa, Jack F. Douglasa, and Kathryn L. Beersa,1 aMaterials Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD 20899 Edited by Krzysztof Matyjaszewski, Carnegie Mellon University, Pittsburgh, PA, and approved January 29, 2020 (received for review September 24, 2019) Uncharged bottlebrush polymer melts and highly charged poly- the exponent λ ranges from 1/3 to 2/5 as backbone length is electrolytes in solution exhibit correlation peaks in scattering increased. A recent simulation study confirmed the finding, λ measurements and simulations. Given the striking superficial of 2/5, in the limit of long backbones (17). Interestingly, similar similarities of these scattering features, there may be a deeper characteristic features are also found in polyelectrolyte solu- structural interrelationship in these chemically different classes of tions and the nature of their origin has triggered an ongoing materials. Correspondingly, we constructed a library of isotopically theoretical discussion, including the origin and meaning of the labeled bottlebrush molecules and measured the bottlebrush so-called “polyelectrolyte peak” observed in scattering mea- correlation peak position q* = 2π=ξ by neutron scattering and in surements (28). The similarity of these two classes of materials simulations. We find that the correlation length scales with the has been noted, although largely in passing (29–31). ξ ∼ c−0.47 backbone concentration, BB , in striking accord with the scaling Here, we take advantage of a variety of polymerizations to of ξ with polymer concentration cP in semidilute polyelectrolyte so- access a library of materials with varying backbone chemistries, ξ ∼ c−1=2 lutions ( P ). -
Lecture1541230922.Pdf
MODULE-1 Introduction: -The macromolecules are divided between biological and non-biological materials. The biological polymers form the very foundation of life and intelligence, and provide much of the food on which man exists. The non-biological polymers are primarily the synthetic materials used for plastics, fibers and elastomers but a few naturally occurring polymers such as rubber wool and cellulose are included in this class. Today these substances are truly indispensable to mankind because these are essential to his clothing,shelter, transportation, communication as well as the conveniences of modern living. Polymer Biological Non- biological Proteins, starch, wool plastics, fibers easterners Note: Polymer is not said to be as macromolecule, because polymer is composedof repeating units whereas the macromolecules may not be composed of repeating units. Definition: A polymer is a large molecule built up by the repetition of small, simple chemical units known as repeating units which are held together by chemical covalent bonds. These repeating units are called monomer Polymer – ---- poly + meres Many parts In some cases, the repetition is linear but in other cases the chains are branched on interconnected to form three dimensional networks. The repeating units of the polymer are usually equivalent on nearly equivalent to the monomer on the starting material from which the polymer is formed. A higher polymer is one in which the number of repeating units is in excess of about 1000 Degree of polymerization (DP): - The no of repeating units or monomer units in the chain of a polymer is called degree of polymerization (DP) . The molecular weight of an addition polymer is the product of the molecular weight of the repeating unit and the degree of polymerization (DP). -
Statistical Properties of Linear-Hyperbranched Graft
Statistical properties of linear-hyperbranched graft copolymers prepared via ”hypergrafting” of ABm monomers from linear B-functional core chains: A Molecular Dynamics simulation Hauke Rabbel,1 Holger Frey,2 and Friederike Schmid3, ∗ 1Leibniz-Institut f¨ur Polymerforschung Dresden e.V., Hohe Straße 6, 01069 Dresden 2Institut f¨ur Organische Chemie, Johannes Gutenberg-Universit¨at Mainz, D-55099 Mainz, Germany 3Institut f¨ur Physik, Johannes Gutenberg-Universit¨at Mainz, D-55099 Mainz, Germany (Dated: June 11, 2018) The reaction of ABm monomers (m = 2, 3) with a multifunctional Bf -type polymer chain (”hy- pergrafting”) is studied by coarse-grained molecular dynamics simulations. The ABm monomers are hypergrafted using the slow monomer addition strategy. Fully dendronized, i.e., perfectly branched polymers are also simulated for comparison. The degree of branching DB of the molecules obtained with the ”hypergrafting’ process critically depends on the rate with which monomers attach to inner monomers compared to terminal monomers. This ratio is more favorable if the ABm monomers have lower reactivity, since the free monomers then have time to diffuse inside the chain. Configurational chain properties are also determined, showing that the stretching of the polymer backbone as a con- sequence of the ”hypergrafting” procedure is much less pronounced than for perfectly dendronized chains. Furthermore, we analyze the scaling of various quantities with molecular weight M for large M (M > 100). The Wiener index scales as M 2.3, which is intermediate between linear chains (M 3) and perfectly branched polymers (M 2 ln(M)). The polymer size, characterized by the radius of ν gyration Rg or the hydrodynamic radius Rh, is found to scale as Rg,h ∝ M with ν ≈ 0.38, which lies between the exponent of diffusion limited aggregation (ν = 0.4) and the mean-field exponent predicted by Konkolewicz and coworkers (ν = 0.33).