RESP atomic charges were derived for the central fragment of N^τ-(1,2,3-trihydroxypropan-2-yl)histidine (HIQ) aminoacid. This modified aminoacid can be found in dihydroxyacetone kinases and structurally-related transcriptional regulators, as the result of the reaction of dihydroxyacetone with a specific histidine residue (Erni et al. Cell. Mol. Life Sci. 63, 890-900, 2006). Other possible names are tele-(1,2,3-trihydroxypropan-2-yl)histidine, 1-[1,2-dihydroxy-1-(hydroxymethyl)ethyl]-L-histidine, Nε2-trihydroxypropan-2-yl-histidine or 1'-(1,2,3-trihydroxyprop-2-yl)-L-histidine.

The atomic charges were derived using two conformations for N-acetyl-N^τ-(1,2,3-trihydroxypropan-2-yl)histidine-N'-methylamide (ACE-HIQ-NME), one close to that found in the α-helix (φ=-80.96, ψ=-17.24) and another to that in the β-sheet (φ=-141.36, ψ=135.44) secondary structure. In both conformations, χ₁ is gauche(-) (χ₁=-59.67 and χ₁=-59.10, respectively). The initial conformation for the ACE-HIQ-NME sidechain was taken from a protein model (by homology with that of Siebold et al. J. Biol. Chem. 278, 48236-44, 2003) in which the trihydroxypropanyl moiety is hydrogen-bonded to other protein residues and makes no intra-residue hydrogen bonds with the substituted histidine. Geometry optimization of the two conformations was performed in Gamess-US, at the Hartree-Fock level of theory using the 6-31G** basis set.

Molecular electrostatic potential (MEP) computation and charge fitting were carried out through the R.E.D. Server. MEP were obtained with Gaussian 03 at the B3LYP/cc-pVTZ theory level (Polarized Continuum Model using the Integral Equation Formalism, mimicking the diethylether environment) and using the Connolly surface algorithm. The molecular orientation of each optimized structure was controlled using the rigid-body re-orientation algorithm, with four orientations being used for each conformation. Charge derivation for the HIQ fragment was carried out by using ACE-HIQ-NME and by setting two intra-molecular charge constraints to zero for the ACE and NME residues during the charge fitting step. A RRMS of 0.13085 was obtained.

The all-atom force field library is suitable for MD simulations using the Duan et al. AMBER force field.