Performance comparison of computational methods for modeling alpha-helical structures

Abstract

Geometry optimization results are reported for secondary structural elements of small proteins and polypeptides. Emphasis is placed on how well molecular mechanics as well as semiempirical, ab initio, and density functional methods describe α-helical and related structures in purely theoretical models (Gly10, Ile10) as well as in realistic models (an α-helical region of calmodulin, and the complete structure of a small protein). Many of the methods examined here were found to provide unsatisfactory descriptions of the hydrogen-bonding interactions within polypeptide-type structures, as the α-helical canonical secondary structure motif was not reproduced accurately. Ab initio and DFT methods provided reasonable results only when solvation models were included, although Hartree-Fock failed even with solvation in one of the test cases; among the semiempirical methods, one of the PM6 implementations performed very well.

Enhanced semiempirical QM methods for biomolecular interactions

“…If non-covalent interactions are essential, SQM-DH based refinement of structures might in general be a good idea [96] . Lupan et al for instance found very good results for α -helical structures [97] , also in comparison to DFT methods. Especially PM6-DH + proved valuable as a basis for the non-local optimization of molecular structures, for instance for screening the conformational space of the FGG tripeptide [98] or DNA quadruplex/molecule complexes [99] .…”

“…Also many other studies both in life and materials science found the performance of SQM-DH methods similar to DFT-D [84,91,92,97,122,143,144,153,161–166] , sometimes even when aiming for high accuracy in complicated cases (like for instance the interaction of DNA bases with Li@C60 [167] ), but a number of studies (often relying on the older AM1-D or PM3-D models) observe a lower quality of SQM-DH results [168–170] .…”

Recent Progress in Treating Protein–Ligand Interactions with Quantum-Mechanical Methods

“…A large number of studies have now shown that SQM-DH methods perform almost as accurately as DFT-D for a wide variety of systems that are dominated by non-covalent interactions [ 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ]. Furthermore, detailed benchmark studies, in comparison to classical approaches, DFT-D, and highly accurate WFT data is available in the original development papers as well as in separate benchmark studies [ 76 ].…”

“…Excellent correlation with experiment was observed, with an R 2 value of 0.9, in comparison to 0.7 for an classical approach. Like DFT-D, SQM-DH methods were shown to be valuable for structure refinement purposes [ 75 , 87 , 88 , 89 , 90 ]. Again, like DFT-D, SQM-DH proved to be an intesting tool for applications in materials science [ 71 , 91 , 92 , 93 , 94 , 95 ], giving some hope for tackling problems at the interface of life and materials science.…”

Microwave‐Assisted Catalytic Amination of Phenothiazine; Reliable Access to Phenothiazine Analogues of Tröger's Base

“…The conformational analysis of the phenothiazine unit (folded along an axis passing through the heteroatoms N and S) indicates a preference for a quasi-equatorial orientation of the methyl substituent, but minima with one or both methyl groups in quasi-axial orientation were also identified (Figure 3), which are higher in energy by 5-12 kcal/mol, depending on the method employed. [39] To elucidate the preferred molecular structures in the solid state, single crystals of PTB 5a and 5b that were suitable for X-ray analysis were obtained from ethanol. [39] To elucidate the preferred molecular structures in the solid state, single crystals of PTB 5a and 5b that were suitable for X-ray analysis were obtained from ethanol.…”