Characteristics of interactions at protein segments without non-local intramolecular contacts in the Protein Data Bank

PLoS One. 2018 Dec 11;13(12):e0205052. doi: 10.1371/journal.pone.0205052. eCollection 2018.


The principle of three-dimensional protein structure formation is a long-standing conundrum in structural biology. A globular domain of a soluble protein is formed by a network of atomic contacts among amino acid residues, but regions without intramolecular non-local contacts are often observed in the protein structure, especially in loop, linker, and peripheral segments with secondary structures. Although these regions can play key roles for protein function as interfaces for intermolecular interactions, their nature remains unclear. Here, we termed protein segments without non-local contacts as floating segments and sought them in tens of thousands of entries in the Protein Data Bank. As a result, we found that 0.72% of residues are in floating segments. Regarding secondary structural elements, coil structures are enriched in floating segments, especially for long segments. Interactions with polypeptides and polynucleotides, but not chemical compounds, are enriched in floating segments. The amino acid preferences of floating segments are similar to those of surface residues, with exceptions; the small side chain amino acids, Gly and Ala, are preferred, and some charged side chains, Arg and His, are disfavored for floating segments compared to surface residues. Our comprehensive characterization of floating segments may provide insights into understanding protein sequence-structure-function relationships.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Protein*
  • Protein Domains
  • Protein Structure, Secondary
  • Proteins / chemistry*
  • Proteins / genetics*
  • Structure-Activity Relationship


  • Proteins

Grant support

This work was supported by the Japan Society for the Promotion of Science KAKENHI, Grant-in-Aid for Young Scientists (Grant Number: JP16K18526).