3d interaction homology: The structurally known rotamers of tyrosine derive from a surprisingly limited set of information-rich hydropathic interaction environments described by maps

ABSTRACT Sidechain rotamer libraries are obtained through exhaustive statistical analysis of existing crystallographic structures of proteins and have been applied in multiple aspects of structural biology, for example, crystallography of relatively low‐resolution structures, in homology model building and in biomolecular NMR. Little is known, however, about the driving forces that lead to the preference or suitability of one rotamer over another. Construction of 3D hydropathic interaction maps for nearly 30,000 tyrosines reveals the environment around each, in terms of hydrophobic (π–π stacking, etc.) and polar (hydrogen bonding, etc.) interactions. After partitioning the tyrosines into backbone‐dependent (ϕ, ψ) bins, a map similarity metric based on the correlation coefficient was applied to each map‐map pair to build matrices suitable for clustering with k‐means. The first bin (−200° ≤ ϕ