A new clustering and nomenclature for beta turns derived from high-resolution protein structures

Protein loops connect regular secondary structures and contain 4-residue beta turns which represent 63% of the residues in loops. The commonly used classification of beta turns (Type I, I', II, II', VIa1, VIa2, VIb, and VIII) was developed in the 1970s and 1980s from analysis of a small number of proteins of average resolution, and represents only two thirds of beta turns observed in proteins (with a generic class Type IV representing the rest). We present a new clustering of beta-turn conformations from a set of 13,030 turns from 1074 ultra-high resolution protein structures (1.2 angstrom). Our clustering is derived from applying the DBSCAN and k-medoids algorithms to this data set with a metric commonly used in directional statistics applied to the set of dihedral angles from the second and third residues of each turn. We define 18 turn types compared to the 8 classical turn types in common use. We propose a new 2-letter nomenclature for all 18 beta-turn types using Ramachandran region names for the two central residues (e.g., A' and D' for alpha regions on the left side of the Ramachandran map and a' and d' for equivalent regions on the right-hand side; classical Type I turns are AD' turns and Type I' turns are ad'). We identify 11 new types of beta turn, 5 of which are sub-types of classical beta-turn types. Up-to-date statistics, probability densities of conformations, and sequence profiles of beta turns in loops were collected and analyzed. A library of turn types, BetaTurnLib18, and cross-platform software, BetaTurnTool18, which identifies turns in an input protein structure, are freely available and redistributable from dunbrack.fccc.edu/betaturn and github.com/sh-maxim/BetaTurn18. Given the ubiquitous nature of beta turns, this comprehensive study updates understanding of beta turns and should also provide useful tools for protein structure determination, refinement, and prediction programs. Author summary Folded proteins consist of elements of regular secondary structure, such as alpha helices and beta sheets connected by irregular structures called loops. Loops have a varying length and typically contain U-shaped beta turns which abruptly change the direction of the chain. Beta turns are formed by four sequential amino acid residues and adopt specific conformations which have been classified into eight types since the 1970s. Based on a larger set of very detailed protein structures and thorough statistical data analysis, the previous set of beta-turn types was revised to include 7 existing turn types, 5 subtypes of the existing turns, and 6 new types. Their properties and amino-acid sequence propensities are analyzed. We propose a self-explanatory turn nomenclature, based on the conformations of residues 2 and 3 of the beta turn, that is much easier to remember than the old nomenclature. We developed a library of 18 turn types and software to assign them to an input protein structure. The software and new turn types should advance fundamental understanding of protein structure as well as benefit applications for protein structure prediction, determination, and refinement.