Reoptimized interaction parameters for the peptide-backbone model compound N-methylacetamide in the GROMOS force field: influence on the folding properties of two beta-peptides in methanol.
Considering N-methylacetamide (NMA) as a model compound, new interaction parameters are developed for the amide function in the GROMOS force field that are compatible with the recently derived 53A6(OXY) parameter set for oxygen-containing chemical functions. The resulting set, referred to as 53A6(OXY+A) , represents an improvement over earlier GROMOS force-field versions in the context of the pure-liquid properties of NMA, including the density, heat of vaporization, dielectric permittivity, self-diffusion constant and viscosity, as well as in terms of the Gibbs hydration free energy of this molecule. Assuming that NMA represents an adequate model compound for the backbone of peptides, 53A6(OXY+A) may be expected to also provide an improved description of polypeptide chains. As an initial test, simulations are reported for two β-peptides characterized by very different folding properties in methanol. For these systems, earlier force-field versions provided good agreement with experimental NMR data, and the test shows that the improved description achieved in the context of NMA is not accompanied by any deterioration in the representation of the conformational properties of these peptides.
Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH, CH-8093 Zürich, Switzerland. bruno.horta@gmail.com
Bruno A C
BA
Horta
Zhixiong
Z
Lin
Wei
W
Huang
Sereina
S
Riniker
Wilfred F
WF
van Gunsteren
Philippe H
PH
Hünenberger
D000081:Acetamides / Q000737:chemistry*; D003198:Computer Simulation; D006860:Hydrogen Bonding; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry*; D011789:Quantum Theory; D013816:Thermodynamics; D014783:Viscosity; D014867:Water / Q000737:chemistry
D000081:Acetamides; D010455:Peptides; D014867:Water; C018595:N-methylacetamide; D000432:Methanol