Significance of Knotted Structures for Function of Proteins and Nucleic Acids - September 17-21, 2014

Significance of Knotted Structures for Function of Proteins and Nucleic Acids

Poster Session II

32 – POS

Board 4

E ff ect of the Tottori Familial Disease Mutation (D7N) on the Monomers and Dimers of Aβ40 and Aβ42 Son Tung Ngo 1,2 , Man Hoang Viet 1 , Phuong H. Nguyen 3 , Philippe Derreumaux 4,5 , Mai Suan Li 1 . 1 Institute of Physics PAN, Warsaw, Poland, 2 Institute for Computational Science and Technology, Ho Chi Minh, Viet Nam, 3 Universite Paris 7, Paris, France, 4 Universite Denis Diderot, Paris, France, 5 Institut Universitaire de France, Paris, France. Recent experiments have shown that the mutation Tottori (D7N) alters the toxicity, assembly and rate of fibril formation of the wild type (WT) amyloid beta (Aβ) Aβ40 and Aβ42 peptides. We used all-atom molecular dynamics simulations in explicit solvent of the monomer and dimer of both alloforms with their WT and D7N sequences. The monomer simulations starting from a random coil and totaling 3 μs show that the D7N mutation changes the fold and the network of salt bridges in both alloforms. The dimer simulations starting from the amyloid fibrillar states and totaling 4.4 μs also reveal noticeable changes in terms of secondary structure, salt bridge, and topology. Overall, this study provides physical insights into the enhanced rate of fibril formation upon D7N mutation and an atomic picture of the D7N-mediated conformational change on Aβ40 and Aβ42 peptides. Board 5 KnotProt: A Database of Proteins with Knots and Slipknots Michal Jamroz 1 , Wanda Niemyska 2 , Eric J. Rawdon 3 , Andrzej Stasiak 4, *, Kenneth C. Millett 5 , Piotr Sułkowski 6, *, and Joanna I. Sulkowska 1,7, * 1 Faculty of Chemistry, University of Warsaw, Warsaw, Poland, 2 Institute of Mathematics, University of Silesia, Katowice, Poland, 3 Department of Mathematics, University of St. Thomas, Saint Paul, USA, 4 Center for Integrative Genomics, University of Lausanne, Switzerland, 5 Department of Mathematics, University of California, Santa Barbara, USA, 6 Faculty of Physics, University of Warsaw, Warsaw, Poland, 7 Centre of New Technologies, University of Warsaw, Warsaw, Poland The protein topology database KnotProt, collects information about protein structures with open polypeptide chains forming knots or slipknots. The knotting complexity of the catalogued proteins is presented in the form of a matrix diagram that shows users the knot type of the entire polypeptide chain and of each of its subchains. The pattern visible in the matrix gives the knotting fingerprint of a given protein and permits users to determine, for example, the minimal length of the knotted regions (knots’ core size) or the depth of a knot, i.e. how many aminoacids can be removed from either end of the catalogued protein structure before converting it from a knot to a different type of knot. In addition, the database presents extensive information about the biological function of proteins with non-trivial knotting and the families and fold types of these proteins. As an additional feature, the KnotProt database enables users to submit protein or polymer structures and generate their knotting fingerprints. 33 – POS

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