First-Principle Computational Study on the Full Conformational Space of l-Threonine Diamide, the Energetic Stability of Cis and Trans Isomers

Abstract

First-principle computations were carried out on the conformational space of trans and cis peptide bond isomers of HCO-Thr-NH2. Using the concept of multidimensional conformational analysis (MDCA), geometry optimizations were performed at the B3LYP/6-31G(d) level of theory, and single-point energies as well as thermodynamic functions were calculated at the G3MP2B3 level of theory for the corresponding optimized structures. Two backbone Ramachandran-type potential energy surfaces (PESs) were computed, one each for the cis and trans isomers, keeping the side chain at the fully extended orientation (chi1=chi2=anti). Similarly, two side chain PESs for the cis and trans isomers were generated for the (phi=psi=anti) orientation corresponding to approximately the betaL backbone conformation. Besides correlating the relative Gibbs free energy of the various stable conformations with the number of stabilizing hydrogen bonds, the process of trans-->cis isomerization is discussed in terms of intrinsic stabilities as measured by the computed thermodynamic functions.

Influence of ionization on the conformational preferences of peptide models. Ramachandran surfaces of N‐formyl‐glycine amide and N‐formyl‐alanine amide radical cations

“…In the last two decades, many Ramachandran maps have been reported for peptide models of glycine and alanine using molecular mechanics, semiempirical methods and ab initio and DFT calculations 2–24. Other studies have analyzed the interplay between the intrinsic backbone properties and the side chain backbone interactions 25–27. However, as far as we know no studies have analyzed the influence of oxidation on these Ramachandran maps, an important aspect considering that this is a common process in the oxidative damage of proteins that may largely influence the intrinsic backbone conformational properties of peptides.…”

First-principle conformational analysis of glycine residues in the αβ-tubulin dimer

“…Owing to the lack of side chains, the glycine residues can rotate with low energy barriers. As shown in Figure 4, more types of hydrogen bonds are resulted in than expected (Sahai et al, 2006); i.e., …”

“…An improved model is constructed with the addition of HCO-and NH 2 − caps at the N and C terminals of amino acids (Hoyau et al, 1997). On basis of the first-principle calculations on the conformational space of HCO-Thr-NH 2 , Sahai et al (Sahai et al, 2006) plotted the backbone Ramachandrantype potential energy surfaces (PES). The third models of protein are polypeptides (Ireta et al, 2005), which are larger than the former two and therefore contain more structural information.…”

“…The third models of protein are polypeptides (Ireta et al, 2005), which are larger than the former two and therefore contain more structural information. As the laws of multidimensional conformational analysis (MDCA) predict, 162 possible conformations arise for the HCO-Thr-NH 2 structure (Sahai et al, 2006). Accordingly, the conformations to be considered will be enormous even for very short polypeptides.…”

Conformational landscape and low lying excited states of imatinib

“…Experimental data, Opt. Optimized; A, B The two forms found in cAbl kinase complexes with IMT [59]; α, β the two structures determined in the α and β polymorphs of imatinib [22] (5) b Not available energies, at least for small or medium-sized molecules [74][75][76][77][78][79][80]. Such properties are somehow Bsystem dependent^, i.e., in some cases the experimentally derived properties are accurately reproduced even with a small basis set like 6-31G(d).…”