Assessing the performance of popular QM methods for calculation of conformational energies of trialanine

Accurate description of the conformational energies of the amino acids is essential for molecular dynamics simulation of protein structures. In this study, we compute the relative energies at 51 conformations for a trialanine tetrapeptide at different levels of theory. The computed energies at various theoretical levels, including the semiempirical DFTB method, HF, DFT, MP2 and CCSD(T), are compared with each other. The calculated energies from density-fitting local CCSD(T)/CBS (complete basis set) calculations are taken as the benchmark. The accuracy of the theoretical methods is highly dependent on the electronic correlation and dispersion corrections as well as the size of the basis sets. The involvement of the empirical dispersion energies in HF and DFT methods consistently improves their performance. Considering both the accuracy and computational efficiency, the Minnesota density functional M06-L-D and M06-2X-D are efficient and accurate for modeling of trialanine structures.