Benchmark Structures and Conformational Landscapes of Amino Acids in the Gas Phase: A Joint Venture of Machine Learning, Quantum Chemistry, and Rotational Spectroscopy

Abstract

The accurate characterization of prototypical bricks of life can strongly benefit from the integration of high resolution spectroscopy and quantum mechanical computations. We have selected a number of representative amino acids (glycine, alanine, serine, cysteine, threonine, aspartic acid and asparagine) to validate a new computational setup rooted in quantum-chemical computations of increasing accuracy guided by machine learning tools. Together with low-lying energy minima, the barriers ruling their interconversion are evaluated in order to unravel possible fast relaxation paths. Vibrational and thermal effects are also included in order to estimate relative free energies at the temperature of interest in the experiment. The spectroscopic parameters of all the most stable conformers predicted by this computational strategy, which do not have low-energy relaxation paths available, closely match those of the species detected in microwave experiments. Together with their intrinsic interest, these accurate results represent ideal benchmarks for more approximate methods.

Accurate Structures and Spectroscopic Parameters of Phenylalanine and Tyrosine in the Gas Phase: A Joint Venture of DFT and Composite Wave-Function Methods

“…Contrary to the usual situation for aliphatic amino acids, conformers of type II are more stable than their types I and I′ counterparts in spite of a less favorable orientation of the OH group in the carboxyl moiety. The increased stability of these conformers is related to the existence of a “daisy chain” sequence of interactions involving aromatic π electrons, together with the NH 2 and OH groups of the backbone .…”

“…Therefore, equilibrium rotational constants require very accurate geometrical parameters, which can be obtained only with state-of-the-art QC methods, − although reasonable relative errors (typically 0.4–0.5%) are obtained at the rDSD level . We have recently shown that the systematic nature of the errors permits to improve significantly the rDSD geometrical parameters, and thus equilibrium rotational constants, by a linear regression approach (hereafter LRA). ,, In this model, the computed geometrical parameters ( r comp ) are corrected for systematic errors by means of scaling factors ( a ) and offset values ( b ) depending on the nature of the involved atoms and determined once for ever from a large database of accurate semiexperimental (SE) equilibrium geometries: ,, r L R A = a × r c o m p + b …”

“…Since at least one 14 N quadrupolar nucleus is present in all amino acids, nuclear quadrupole coupling constants (χ ii , with i referring to the inertia axis a , b , or c ) are important for accurate predictions of rotational spectra because they determine a splitting of the rotational transitions, which generates the so-called hyperfine structure. , Furthermore, the components of dipole moments (μ i ) determine the intensities of rotational transitions. , Several studies have shown that dipole moments and quadrupole coupling constants can be computed with sufficient accuracy at the rDSD level. , On the other hand, accurate electronic energies can be obtained by single-point energy evaluations at rDSD geometries using composite wave function methods rooted in the coupled cluster (CC) ansatz . In particular, the CC model including single, double, and perturbative estimate of triple excitations (CCSD­(T)) is employed here taking also into account complete basis set (CBS) extrapolation and core valence (CV) correlation.…”

“…This procedure has been recently validated for several amino acids containing polar side chains. − Here we tackle the problem of aromatic side chains analyzing both the rotational and vibrational spectra of the prototypical phenylalanine and tyrosine amino acids. In fact, previous studies of these amino acids employed QC methods of limited accuracy, payed marginal attention to the geometrical parameters and neglected vibrational corrections beyond the standard rigid rotor harmonic oscillator (RRHO) model.…”

Protonation of serine: conformers, proton affinities and gas-phase basicities at the “gold standard” and beyond

“…9,17,23,24 From the theoretical side, many authors have been involved in the search for serine and protonated serine conformers. 14,[25][26][27][28][29][30][31][32][33][34] For neutral serine, we found the one published by He and Allen 25 to be the highest in terms of the level of theory and in the number of conformers found. They systematically mapped the conformational space with rotating the most flexible parts of the molecule, and performed geometry optimizations at the RHF/6-31G* level.…”