RESP atomic charges embedded in force field libraries for the
N-Acetyl-β-carboxylato-
L-aspartate-
N'-methylamide dipeptide (or ACE-GLA-NME capped amino acid), as well as for the central, (+)NH3-terminal and (-)OOC-terminal fragments of the β-carboxylato-
L-aspartate amino acid. All atom force field libraries suitable for MD simulations using the Cornell
et al. AMBER force field (and/or its successive adaptations: Kollman
et al., Cheatham
et al., Wang
et al. & Hornak
et al. force fields). A single conformation for the
N-Acetyl-β-carboxylato-
L-aspartate-
N'-methylamide dipeptide (φ = -68.7, ψ = 157.0, χ = -97.0) was considered in the procedure.
Charge derivation and force field library building for the central fragment of β-carboxylato-
L-aspartate (or GLA fragment) were carried out by using
N-Acetyl-β-carboxylato-
L-aspartate-
N'-methylamide, and setting two intra-molecular charge constraints to a value of zero for the ACE and NME residues during the charge fitting step. Charge derivation and force field library building for the
N-terminal fragment of β-carboxylato-
L-aspartate (or NGLA fragment) were performed by using two molecules: methylammonium and
N-Acetyl-β-carboxylato-
L-aspartate-
N'-methylamide, and setting two different constraints to a value of zero during the fitting step: (i) an inter-molecular charge constraint between the methyl group of methylammonium and the CH3CO-NH group of atoms of the capped amino acid, and (ii) an intra-molecular charge constraint for the NME residue of the capped amino acid. Charge derivation and force field library building for the
C-terminal fragment of β-carboxylato-
L-aspartate (or CGLA fragment) were carried out by using two molecules: acetate and
N-Acetyl-β-carboxylato-
L-aspartate-
N'-methylamide, and setting to a value of zero two different constraints during the fitting step: (i) an inter-molecular charge constraint between the methyl group of acetate and the CO-NHCH3 group of atoms of the capped amino acid, and (ii) an intra-molecular charge constraint for the ACE residue of the capped amino acid (Scheme 1).
Scheme 1
Multiple orientation single conformation and multiple molecule charge derivation and force field library building for the N-Acetyl-β-carboxylato-L-aspartate-N'-methylamide dipeptide and the corresponding central, H3N(+)-terminal and (-)OOC-terminal molecular fragments carried out using R.E.D. Server and the R.E.D. IV program. (A) Description of the different molecules involved in the procedure. Dashed line box: symbolisation of intra-molecular charge constraints used during the fitting step within the dipeptide; Plain line box: symbolisation of inter-molecular charge constraints used during the fitting step between the dipeptide and methylammonium or acetate. ACE chemical group = CH3CO; NME chemical group = NHCH3. (B) Selection of force field libraries generated in the Tripos mol2 file format.
Geometry optimization, frequency calculation and molecular electrostatic potential (MEP) computation were carried out using the Gaussian 03 program, while charge fitting was performed using the RESP program. For all the structures, the HF method and the 6-31G* basis set in gas phase were used in geometry optimization and frequency calculation. MEP computation was carried out using the HF/6-31G* theory level in gas phase, and the Connolly surface algorithm. The molecular orientation of each optimized structure was controlled using the rigid-body re-orientation algorithm implemented in the R.E.D. program. Four molecular orientations for
N-Acetyl-β-carboxylato-
L-aspartate-
N'-methylamide (based on the GLA nitrogen, GLA α-carbon, GLA β-carbon; GLA β-carbon, GLA α-carbon, GLA nitrogen; GLA nitrogen, GLA α-carbon, GLA carbonyl-carbon; GLA carbonyl-carbon, GLA α-carbon, GLA nitrogen atoms), and two molecular orientations for methylammonium (based on the methyl carbon, nitrogen, anti nitrogen hydrogen atoms; anti nitrogen hydrogen, nitrogen, methyl carbon atoms) and acetate (based on the methyl carbon, carboxylatolate carbon, terminal oxygen atoms; terminal oxygen, carboxylatolate carbon, methyl carbon atoms)] were involved in MEP computation. A RRMS (relative root mean square value between the MEP values calculated by quantum mechanics, and those generated using the derived charge values) of 0.011 was obtained for the fitting step.