Fragment Localized Molecular Orbitals

Abstract

We introduce the concept of fragment localized molecular orbitals (FLMOs), which are Hartree-Fock molecular orbitals localized in specific fragments constituting a molecular system. In physical terms, we minimize the local electronic energies of the different fragments, at the cost of maximizing the repulsion between them. To showcase the approach, we rationalize the main interactions occurring in large biological systems in terms of interactions between the fragments of the system. In particular, we study an anticancer drug intercalated within DNA and retinal in anabaena sensory rhodopsin as prototypes of molecular systems embedded in biological matrixes. Finally, the FLMOs are exploited to rationalize the formation of two oligomers, prototypes of amyloid diseases, such as Parkinson and Alzheimer.

Figure 1

(a) Molecular structure of the studied drug (XR5944). (b) XR5944 intercalated within DNA (PDB 1X95), (c) the exploited fragmentation, and (d) the fragment densities obtained by using the FLMOs procedure. (e) FLMOs interaction energy decomposition analysis (kcal/mol).

Figure 2

Graphical representation of the most important FLMOs interactions for all the studied fragment couples (top, frag₁-helix_1,2; middle, frag₃-helix_1,2; bottom, top: frag₂-helix_1,2).

Figure 3

(a) Molecular structure of all-trans retinal chromophore embedded in the closest 14 amino acids of the anabaena sensory rhodopsin. (b) FLMOs interaction energy decomposition analysis (kcal/mol). (c) Graphical representation of the most important FLMOs interactions between retinal and the 14 selected amino acids.

Figure 4

Molecular structures of the selected amyloid peptide prototypes (a–d) and their three-dimensional arrangements (b–e). FLMOs interaction energy decomposition analysis (parts c–f, kcal/mol).