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Molecular design of specific metal-binding peptide sequences from protein fragments: Theory and experiment

Kozisek, Milan; Svatos, Ales; Budesinsky, Milos; Muck, Alexander; Bauer, Mikael LU ; Kotrba, Pavel; Ruml, Tomas; Havlas, Zdenek; Linse, Sara LU and Rulisek, Lubomir (2008) In Chemistry: A European Journal 14(26). p.7836-7846
Abstract
A novel strategy is presented for designing peptides with specific metal-ion chelation sites, based on linking computationally predicted ion-specific combinations of amino acid side chains coordinated at the vertices of the desired coordination polyhedron into a single polypeptide chain. With this aim, a series of computer programs have been written that 1) creates a structural combinatorial library containing Z(i)-(X)(n)-Z(j) sequences (n = 0-14; Z: amino acid that binds the metal through the side chain; X: any amino acid) from the existing protein structures in the non-redundant Protein Data Bank; 2) merges these fragments into a single Z(1)-(X)(n1)-Z(2)-(X)(n2)-Z(3)-(X)(n3)- ... -Z(j) polypeptide chain; and 3) automatically performs two... (More)
A novel strategy is presented for designing peptides with specific metal-ion chelation sites, based on linking computationally predicted ion-specific combinations of amino acid side chains coordinated at the vertices of the desired coordination polyhedron into a single polypeptide chain. With this aim, a series of computer programs have been written that 1) creates a structural combinatorial library containing Z(i)-(X)(n)-Z(j) sequences (n = 0-14; Z: amino acid that binds the metal through the side chain; X: any amino acid) from the existing protein structures in the non-redundant Protein Data Bank; 2) merges these fragments into a single Z(1)-(X)(n1)-Z(2)-(X)(n2)-Z(3)-(X)(n3)- ... -Z(j) polypeptide chain; and 3) automatically performs two simple molecular mechanics calculations that make it possible to estimate the internal strain in the newly designed peptide. The application of this procedure for the Most M2+-specific combinations of amino acid side chains (M: metal see L. Rulisek, Z. Havlas J. Phys. Chem. B 2003, 107, 2376-2385) yielded several peptide sequences (with lengths of 6-20 amino acids) with the potential for specific binding with six metal ions (Co2+, Ni2+, Cu2+, Zn2+, Cd2+ and Hg2+). The gas-phase association constants of the studied metal ions with these de novo designed peptides were experimentally determined by MALDI mass spectrometry by using 3,4,5-trihydroxyacetophenone as a matrix, whereas the thermodynamic parameters of the metal-ion coordination in the condensed phase were measured by isothermal titration calorimetry (ITC), chelatometry and NMR spectroscopy methods. The data indicate that some of the computationally predicted peptides are potential M2+-specific metalion chelators. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
peptides, molecular design, metal-ion chelation, ab initic calculations, mass spectrometry
in
Chemistry: A European Journal
volume
14
issue
26
pages
7836 - 7846
publisher
John Wiley & Sons
external identifiers
  • wos:000259523500015
  • scopus:53849109609
ISSN
1521-3765
DOI
10.1002/chem.200800178
language
English
LU publication?
yes
id
46718f0b-ede6-4164-bcbb-e6e1f886cf05 (old id 1286788)
date added to LUP
2009-01-29 15:51:07
date last changed
2017-01-01 05:40:31
@article{46718f0b-ede6-4164-bcbb-e6e1f886cf05,
  abstract     = {A novel strategy is presented for designing peptides with specific metal-ion chelation sites, based on linking computationally predicted ion-specific combinations of amino acid side chains coordinated at the vertices of the desired coordination polyhedron into a single polypeptide chain. With this aim, a series of computer programs have been written that 1) creates a structural combinatorial library containing Z(i)-(X)(n)-Z(j) sequences (n = 0-14; Z: amino acid that binds the metal through the side chain; X: any amino acid) from the existing protein structures in the non-redundant Protein Data Bank; 2) merges these fragments into a single Z(1)-(X)(n1)-Z(2)-(X)(n2)-Z(3)-(X)(n3)- ... -Z(j) polypeptide chain; and 3) automatically performs two simple molecular mechanics calculations that make it possible to estimate the internal strain in the newly designed peptide. The application of this procedure for the Most M2+-specific combinations of amino acid side chains (M: metal see L. Rulisek, Z. Havlas J. Phys. Chem. B 2003, 107, 2376-2385) yielded several peptide sequences (with lengths of 6-20 amino acids) with the potential for specific binding with six metal ions (Co2+, Ni2+, Cu2+, Zn2+, Cd2+ and Hg2+). The gas-phase association constants of the studied metal ions with these de novo designed peptides were experimentally determined by MALDI mass spectrometry by using 3,4,5-trihydroxyacetophenone as a matrix, whereas the thermodynamic parameters of the metal-ion coordination in the condensed phase were measured by isothermal titration calorimetry (ITC), chelatometry and NMR spectroscopy methods. The data indicate that some of the computationally predicted peptides are potential M2+-specific metalion chelators.},
  author       = {Kozisek, Milan and Svatos, Ales and Budesinsky, Milos and Muck, Alexander and Bauer, Mikael and Kotrba, Pavel and Ruml, Tomas and Havlas, Zdenek and Linse, Sara and Rulisek, Lubomir},
  issn         = {1521-3765},
  keyword      = {peptides,molecular design,metal-ion chelation,ab initic calculations,mass spectrometry},
  language     = {eng},
  number       = {26},
  pages        = {7836--7846},
  publisher    = {John Wiley & Sons},
  series       = {Chemistry: A European Journal},
  title        = {Molecular design of specific metal-binding peptide sequences from protein fragments: Theory and experiment},
  url          = {http://dx.doi.org/10.1002/chem.200800178},
  volume       = {14},
  year         = {2008},
}