Modelling the Interactions of Protein Side-Chains

摘要

The study of small model molecules containing the relevant functional groups can help us to understand the interactions between side-chains In proteins. Ab initio quantum chemical techniques allow the interactions between the model molecules to be studied with much greater accuracy than is possible for an entire protein, where the use of simple empirical potentials is the norm. In particular, the use of ab initio methods on model molecules permits us to incorporate the atom-atom anisotropic directionality of these interactions. We survey various methods of obtaining the components of the ab initio interaction energy. These are then applied to three systems of biological interest. The first of these is the arginine/aspartate pair found in salt bridges, which involves hydrogen bonding between two charged species. Secondly, we look at the arginine/phosphotyrosine interaction found in complexes between SH2 domains and peptide ligands: here we find that the arginine/phosphate part of the interaction isenergetically far more important than the arginine/aromatic part. Finally, we describe a detailed study of ami no/aromatic interactions in proteins: 'unconventional hydrogen bonds' are found to be remarkably uncommon relative to stacked geometries, and the reasons for this are examined.