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.
33 – POS
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.
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