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Molecular Dynamics Simulations of 441 Two-Residue Peptides in Aqueous Solution: Conformational Preferences and Neighboring Residue Effects with the Amber ff99SB-ildn-NMR Force Field
Journal article   Peer reviewed

Molecular Dynamics Simulations of 441 Two-Residue Peptides in Aqueous Solution: Conformational Preferences and Neighboring Residue Effects with the Amber ff99SB-ildn-NMR Force Field

Shuxiang Li, Casey T Andrews, Tamara Frembgen-Kesner, Mark S Miller, Stephen L Siemonsma, Timothy D Collingsworth, Isaac T Rockafellow, Nguyet Anh Ngo, Brady A Campbell, Reid F Brown, …
Journal of chemical theory and computation, Vol.11(3), pp.1315-1329
03/10/2015
DOI: 10.1021/ct5010966
PMCID: PMC4656151
PMID: 26579777

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Abstract

Understanding the intrinsic conformational preferences of amino acids and the extent to which they are modulated by neighboring residues is a key issue for developing predictive models of protein folding and stability. Here we present the results of 441 independent explicit-solvent MD simulations of all possible two-residue peptides that contain the 20 standard amino acids with histidine modeled in both its neutral and protonated states. (3)J(HNHα) coupling constants and δ(Hα) chemical shifts calculated from the MD simulations correlate quite well with recently published experimental measurements for a corresponding set of two-residue peptides. Neighboring residue effects (NREs) on the average (3)J(HNHα) and δ(Hα) values of adjacent residues are also reasonably well reproduced, with the large NREs exerted experimentally by aromatic residues, in particular, being accurately captured. NREs on the secondary structure preferences of adjacent amino acids have been computed and compared with corresponding effects observed in a coil library and the average β-turn preferences of all amino acid types have been determined. Finally, the intrinsic conformational preferences of histidine, and its NREs on the conformational preferences of adjacent residues, are both shown to be strongly affected by the protonation state of the imidazole ring.
Peptides - chemistry Solutions Water - chemistry Amino Acids - chemistry Nuclear Magnetic Resonance, Biomolecular Protein Conformation Molecular Dynamics Simulation

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