Solvation effects on alanine dipeptide: A MP2/cc‐pVTZ//MP2/6‐31G** study of (Φ, Ψ) energy maps and conformers in the gas phase, ether, and water

Abstract

The effects of solvation on the conformations and energies of alanine dipeptide (AD) have been studied by ab initio calculations up to MP2/cc-pVTZ//MP2/6-31G**, utilizing the polarizable continuum model (PCM) to mimic solvation effects. The energy surfaces in the gas phase, ether, and water bear similar topological features carved by the steric hindrance, but the details differ significantly due to the solvent effects. The gas-phase energy map is qualitatively consistent with the Ramachandran plot showing seven energy minima. With respect to the gas-phase map, the significant changes of the aqueous map include (1) the expanded low-energy regions, (2) the emergence of an energy barrier between C5-beta and alpha(R)-beta(2) regions, (3) a clearly pronounced alpha(R) minimum, a new beta-conformer, and the disappearance of the gas-phase global minimum, and (4) the shift of the dominant region in LEII from the gas-phase C7(ax) region to the alpha(L) region. These changes bring the map in water to be much closer to the Ramachandran plot than the gas-phase map. The solvent effects on the geometries include the elongation of the exposed N-H and C=O bonds, the shortening of the buried HN--CO peptide bonds, and the enhanced planarity of the peptide bonds. The energy surface in ether has features similar to those both in the gas phase and in water. The free energy order computed in the gas phase and in ether is in good agreement with experimental studies that concluded that C5 and C7(eq) are the dominant species in both the gas phase and nonpolar solvents. The free energy order in water is consistent with the experimental observation that the dominant C7(eq) in the nonpolar solvent was largely replaced by P(II)-like (i.e., beta) and alpha(R) in the strong polar solvents. Based on calculations on AD + 4H(2)O and other AD-water clusters, we suggest that explicit water-AD interactions may distort C5 and beta (or alpha(R) and beta) to an intermediate conformation. Our analysis also shows that the PCM calculations at the MP2/cc-pVTZ//MP2/6-31G** level give good descriptions to the bulk solvent polarization effect. The results presented in this article should be of sufficient quality to characterize the peptide bonds in the gas phase and solvents. The energy surfaces may serve as the basis for developing of strategies enabling the inclusion of solvent polarization in the force field.

Efficient model chemistries for peptides. I. General framework and a study of the heterolevel approximation in RHF and MP2 with Pople split‐valence basis sets

“…2 ), < t / point > (hours) that 6-31++G(d) is as efficient as the most efficient basis sets of the rules-complying group (being outperformed only by some of the ones in the third group in table 2), that 6-31 · +G(d,p) has drifted a little towards the inefficiency region and that that 6-31++G( · ,p) is well deep in it. This suggests that it may be profitable to break rule (ii) but only in the direction of removing shells from the hydrogens, and not from the 1st-row atoms; in agreement with the common practice in the literature [6,16,20,22,27,29,31,32,93,97] based on the intuition that 'hydrogens are typically more passive atoms sitting at the end of bonds' [56]. On the other hand, 6-31G(f,d) turns out to be very inefficient, being about as accurate as the simple 6-31G basis set but far more expensive.…”

“…Remarkably, some of this heterolevel MCs, such as 6-311++G(2df,2pd)//6-31+G(d) for example, are physically equivalent to the reference homolevel up to peptides of ten thousand residues at less of 10% the computational cost. Indeed, all these results confirm the heterolevel assumption, discussed in the introduction and so commonly used in the literature [14,29,31,32,46,59,63,64,90], for RHF//RHF-intramethod MCs.…”

“…This is why, the most frequently studied peptides are the shortest ones: the dipeptides [13][14][15][16][17], in which a single amino acid residue is capped at both the N-and C-termini with neutral peptide groups. Among them, the most popular choice has been the alanine dipeptide [9,14,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33], which, being the simplest chiral residue, shares many similarities with most of the rest of dipeptides for the minimum computational price.…”

“…The heterolevel assumption is very commonly assumed in the literature [14,29,31,32,46,59,63,64,90], but it is seldom checked. As far as we know, the only tests for peptides or related systems, have been performed using a small number of conformers [9,15,17,23,91], and this is the first time that this potentially very economical approximation is tested in full PESs.…”

Implementation of the SCC-DFTB Method for Hybrid QM/MM Simulations within the Amber Molecular Dynamics Package

“…Recent experimental results suggest that the backbone preferences in proteins are already present in blocked aminoacids. 55,56 A number of experimental 55,[57][58][59][60] and theoretical, [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78] studies indicate that the potential energy surface for AD in vacuum and in solution are considerably different: While in the gas-phase the global minimum is believed to be a C7 eq structure (ϕ− 83°, ψ~73°), 70 interaction with water favors the polyproline-II (P II , (ϕ~−75°, ψ~150°) conformation. 60 AD has also been used previously to investigate the performance of the SCC-DFTB method as compared to different classical force fields.…”