Evolutionary information hidden in a single protein structure
Related Experiment Video
Updated: May 23, 2026

Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Chien-Hua Shih1, Chih-Min Chang, Yeong-Shin Lin
1Institute of Bioinformatics, National Chiao Tung University, HsinChu 30050, Taiwan, Republic of China.
Abstract:
The knowledge of conserved sequences in proteins is valuable in identifying functionally or structurally important residues. Generating the conservation profile of a sequence requires aligning families of homologous sequences and having knowledge of their evolutionary relationships. Here, we report that the conservation profile at the residue level can be quantitatively derived from a single protein structure with only backbone information. We found that the reciprocal packing density profiles of protein structures closely resemble their sequence conservation profiles. For a set of 554 nonhomologous enzymes, 74% (408/554) of the proteins have a correlation coefficient > 0.5 between these two profiles. Our results indicate that the three-dimensional structure, instead of being a mere scaffold for positioning amino acid residues, exerts such strong evolutionary constraints on the residues of the protein that its profile of sequence conservation essentially reflects that of its structural characteristics.
Related Concept Videos
Conservation of Protein Domains Over Different Proteins
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Protein Organization
The primary structure of a protein is its amino acid sequence.
Protein Organization
Protein Organization
The primary structure of a protein is its amino acid sequence.

