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2006 | 53 | 1 | 121-130
Article title

Free energy of helix propagation in short polyalanine chains determined from peptide growth simulations of La3+-binding model peptides. Comparison with experimental data

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EN
Abstracts
EN
Molecular dynamics (MD) is, at present, a unique tool making it possible to study, at the atomic level, conformational transitions in peptides and proteins. Nevertheless, because MD calculations are always based on a more or less approximate physical model, using a set of approximate parameters, their reliability must be tested by comparison with experimental data. Unfortunately, it is very difficult to find a peptide system in which conformational transitions can be studied both experimentally and using MD simulations so that a direct comparison of the results obtained in both ways could be made. Such a system, containing a rigid α-helix nucleus stabilized by La3+ coordination to a 12-residue sequence taken from an EF-hand protein has recently been used to determine experimentally the helix propagation parameters in very short polyalanine segments (Goch et al. (2003) Biochemistry 42: 6840-6847). The same parameters were calculated here for the same peptide system using the peptide growth simulation method with, alternatively, charmm 22 and cedar potential energy functions. The calculated free energies of the helix-coil transition are about two times too large for cedar and even three times too large for charmm 22, as compared with the experimental values. We suggest that these discrepancies have their origin in the incorrect representation of unfolded peptide backbone in solution by the molecular mechanics force fields.
Publisher

Year
Volume
53
Issue
1
Pages
121-130
Physical description
Dates
published
2006
received
2005-04-19
revised
2005-11-14
accepted
2005-11-16
(unknown)
2005-12-21
Contributors
  • Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, Poland
author
  • Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, USA
  • Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warszawa, Poland
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Document Type
Publication order reference
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YADDA identifier
bwmeta1.element.bwnjournal-article-abpv53p121kz
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