Publication
Identification of the most stable structure(s) of a system is a prerequisite for the calculation of any of its properties from first-principles. However, even for relatively small molecules, exhaustive explorations of the potential energy surface (PES) are severely hampered by the dimensionality bottleneck. In this work, we address the challenging task of efficiently sampling realistic low-lying peptide coordinates by resorting to a surrogate based genetic algorithm (GA)/density functional theory (DFT) approach (sGADFT) in which promising candidates provided by the GA are ultimately optimized with DFT. We provide a benchmark of several computational methods (GAFF, AMOEBApro13, PM6, PM7, DFTB3-D3(BJ)) as possible prescanning surrogates and apply sGADFT to two test case systems that are (i) two isomer families of the protonated Gly-Pro-Gly-Gly tetrapeptide (Masson, A.; et al.J. Am. Soc. Mass Spectrom.2015, 26, 1444-1454) and (ii) the doubly protonated cyclic decapeptide gramicidin S (Nagornova, N. S.; et al.J. Am. Chem. Soc.2010, 132, 4040-4041). We show that our GA procedure can correctly identify low-energy minima in as little as a few hours. Subsequent refinement of surrogate low -energy structures within a given energy threshold (