An improved AMBER force field for α,α-dialkylated peptides: intrinsic and solvent-induced conformational preferences of model systems

• DOI: 10.1039/c3cp52721b
• Publication Date: 2013-08-19T15:07:34Z
• Authors: Sonja Grubišić; Giuseppe Brancato; Vincenzo Barone
• Keywords: Force Field; Side chain

α,α-Dialkylated amino acid residues have acquired considerable importance as effective means for introducing backbone conformation constraints in synthetic peptides. The prototype of such a class residues, namely Aib (α-aminoisobutyric acid), appears to play dominant role determining the preferred conformations host proteins. We recently introduced into standard AMBER force field some new parameters, fitted against high-level quantum mechanical (QM) data, simulating peptides containing α,α-dialkylated with cyclic side chains, TOAC (TOAC, 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) and Ac6c (Ac6c = 1-aminocyclohexaneacetic acid). Here, we show that order accurately reproduce observed conformational geometries structural fluctuations linear based on Aib, further improvements non-bonding chain torsion potential parameters be considered, due expected larger flexibility respect ones. To this end, present an extended set which been optimized by fitting energies multiple dipeptide analogue corresponding QM calculations properly account dispersion interactions (B3LYP-D3). quality, transferability size-consistency proposed assessed both considering series poly-Aib peptides, modeled at same level, performing molecular dynamics simulations solvents high low polarity. As result, allow one good reliability available experimental thus representing notable improvement over current especially description α/310-helix equilibria chains.