Structural Stability in Dimer and Tetramer Clusters of l-Alanine in the Gas Phase and the Feasibility of Peptide Bond Formation

Abstract

Stability in low-energy structures of the dimer and tetramer clusters of l-alanine in the gas phase is studied by accurate quantum chemical computations at the DLPNO2013-CCSD(T) level. It is found that the dispersion interaction energies in the dimer (-0.3 to -0.6 kcal/mol) and in the tetramer (-1.3 to -2.5 kcal/mol) have a small role in the stability of the clusters as compared to the hydrogen bond (HB) energies -4.1 to -14.2 and -32.2 to -40.1 kcal/mol, respectively. The HB energy in the alanine cluster is obtained from the binding energy (BE) of DLPNO2013-CCSD(T)//B2PLYP/def2-TZVP by subtracting the dispersion interaction energy. Local HB energies deduced from the dimer structures are found to be suitable to estimate total HB energies in similar environments. The BEs of OH···NH and OH···OC bonds are -9.5 and -7.1 kcal/mol, respectively. This suggests that the higher clusters are formed through OH···NH bonds as they confer more stability. Analysis of bonding in the tetramer shows that the low-energy tetramer and higher clusters are formed through the OH···NH mode of hydrogen bonding, unlike the dimer which is formed through the OH···OC bond. Feasibility of the amino acid cluster to function as a precursor for polypeptide formation is examined because the orientation of the OH···NH mode of hydrogen bonding is suitable for chemical condensation. The propensity of forming coiled structures in higher clusters and thus in the polypeptides is examined based on the conformational stability in the tetramer of alanine.

A Comprehensive Picture of the Structures, Energies, and Bonding in the Alanine Dimers

“…There are studies dealing with the structures and energies of Alanine dimers [46] . A remarkable observation drawn from Table 2 is that Alanine dimers are strongly bound: the DLPNO‐CCSDT binding energy with B3LYP−D3 ZPE corrections for the degenerate global minimum is 17.2 kcal mol −1 .…”

“…For comparison, the water dimer, the archetypal hydrogen bonded system is reported to be stabilized by 5.5 kcal mol −1 with respect to the isolated monomers at the same DLNPO‐CCSD(T) level of theory and the CCSD(T) binding energies of the carbonic and formic acid dimers are 19.0 and 12.83 kcal mol −1 , respectively [47,48] . Accurate treatment of electron correlation is of crucial importance to calculate binding energies: [46] reported 14.61 kcal mol −1 at the DLNPO‐CCSD(T)/def2‐TZVP//B3LYP/6–311++G( d,p ) for their global minimum; pure B3LYP−D3/6–311++G( d,p ) binding energies calculated here sensibly depart from that number at 20.9 kcal mol −1 for the degenerate global minimum, and our own DLNPO‐CCSD(T)//B3LYP−D3 binding energies are 17.2 kcal mol −1 using the 6–311++G( d,p ) basis set, however, accounting for the basis set superposition error via the counterpoise corrections of Boys and Bernardi [49] yields 13.4 kcal mol −1 , which is substantially closer to the values reported by and to the experimental binding energies of common carboxylic acid dimers, i. e., to the 14.2 kcal mol −1 reported for the dissociation of the formic acid dimer, [50] which exhibits the exact same stabilizing pattern as the global minimum of the alanine dimers. The collective results exposed in Table 2 and Table S2 serve as a cautionary note on the need to accurately treat both, correlation and basis set superposition error effects if meaningful interaction energies are to be obtained.…”

“…There are studies dealing with the structures and energies of Alanine dimers. [46] A remarkable observation drawn from Table 2 is that Alanine dimers are strongly bound: the DLPNO-CCSDT binding energy with B3LYPÀ D3 ZPE corrections for the degenerate global minimum is 17.2 kcal mol À 1 . For comparison, the water dimer, the archetypal hydrogen bonded system is reported to be stabilized by 5.5 kcal mol À 1 with respect to the isolated monomers at the same DLNPO-CCSD(T) level of theory and the CCSD(T) binding energies of the carbonic and formic acid dimers are 19.0 and 12.83 kcal mol À 1 , respectively.…”

“…For comparison, the water dimer, the archetypal hydrogen bonded system is reported to be stabilized by 5.5 kcal mol À 1 with respect to the isolated monomers at the same DLNPO-CCSD(T) level of theory and the CCSD(T) binding energies of the carbonic and formic acid dimers are 19.0 and 12.83 kcal mol À 1 , respectively. [47,48] Accurate treatment of electron correlation is of crucial importance to calculate binding energies: [46] reported 14.61 kcal mol À 1 at the DLNPO-CCSD(T)/def2-TZVP//B3LYP/6-311 + + G(d,p) for Table 1. Properties of the 32 types of intermolecular interactions stabilizing the Alanine dimers (Figure 2).…”

Polypeptide formation in clusters of β-alanine amino acids by single ion impact

“…Recently, several theoretical and experimental studies have been performed in order to answer this question. Amino acid clusters (dimer and tetramer clusters of α-alanine) have been studied by theory as precursors for polypeptide formation as the orientation of the OH ⋯ NH mode of hydrogen bonding is found to be suitable for chemical condensation 15 . In the case of two glycine molecules 16 or double amino acids 17 , different mechanisms for peptide bond formation have been mapped out with quantum mechanical electronic structure methods.…”