2022  1,200
2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 44(2010) N 6 p. 958-967;
A.N. Istrate1, A.B. Mantsyzov1, S.A. Kozin2,3, V.I. Polshakov4*

Optimization of the Methods for Small Peptide Solution Structure Determination by NMR Spectroscopy

1Department of Chemistry, Moscow State University, Moscow, 119992 Russia
2Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Moscow, 119121 Russia
3Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
4Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, Moscow, 119991 Russia

Received - 2010-06-29; Accepted - 2010-06-29

NMR spectroscopy was recognized as a method of protein structure determination in solution. However, determination of the conformation of small peptides, which undergo fast molecular motions, remains a challenge. This is mainly caused by the impossibility to collect the required quantity of the distance and dihedral angle restraints from NMR spectra. At the same time, short charged peptides play an important role in a number of biological processes, in particular in pathogenesis of neurodegenerative diseases including Alzheimer's disease. Therefore, development of a method for structure simulation of small peptides in aqueous environment using the most realistic force fields seems to be of current importance. Such algorithm has been developed using the Amber-03 force field and Gromacs program after modification of its code. Calculation algorithm has been verified on a model peptide with a known solution structure and a metal-binding fragment of rat β-amyloid, whose structure has been determined by alternative methods. The developed algorithm substantially increases structure quality, in particular Ramachandran plot statistics, and decreases RMSD of atomic coordinates inside the calculated family. The described protocol can be used for determination of conformation of short peptides, and also for optimization of structure of larger proteins containing poorly structured fragments.

NMR spectroscopy, molecular dynamics, peptide structure, β-amyloid, Alzheimer disease