Amino acid pair interchanges at spatially conserved locations

Dalit Naor, Daniel Fischer, Robert L. Jernigan, Haim J. Wolfson, Ruth Nussinov

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Here we study the pattern of amino acid pair interchanges at spatially, locally conserved regions in globally dissimilar and unrelated proteins. By using a method which completely separates the amino acid sequence from its respective structure, this work addresses the question of which properties of the amino acids are the most crucial for the stability of conserved structural motifs. The proteins are taken from a structurally non-redundant dataset. The spatially conserved substructural motifs are defined as consisting of a 'large enough' number of C(α) atoms found to provide a geometric match between two proteins, regardless of the order of the C(α) atoms in the sequence, or of the sequence composition of the substructures. This approach can apply to proteins with little or no sequence similarity but with sufficient structural similarity, and is unique in its ability to handle local, non-topological matches between pairs of dissimilar proteins. The method uses a computer-vision based algorithm, the Geometric Hashing. Since the Geometric Hashing ignores sequence information it lends itself to answer the quest-ion posed above. The interchanges at geometrically similar positions that have been obtained with our method demonstrate the expected behaviour. Yet, a closer inspection reveals some distinct characteristics, as compared with interchanges based upon sequence-order based techniques, or from energy-contact-based considerations. First, a pronounced division of the amino acids into two classes is displayed: Lys, Glu, Arg, Gln, Asp, Asn, Pro, Gly, Thr, Ser and His on the one hand, and Ile, Val, Leu, Phe, Met, Tyr, Trp, Cys and Ala on the other. These groups further cluster into subgroups: Lys, Glu, Arg, Gin; Asp Asn; Pro, Gly; Ile, Val, Leu, Phe. The other amino acids stand alone. Analysis of the conservation among amino acids indicates proline to be consistently, by far, the most conserved. Next are Asp, Glu, Lys and Gly. Cys is also highly conserved. Interestingly, oppositely charged amino acids are interchanged roughly as frequently as those of the same charge. These observations can be explained in terms of the three-dimensional structures of the proteins. Most of all, there is a clear distinction between residues which prefer to be on the protein surfaces, compared to those frequently buried in the interiors. Analysis of the interchanges indicates their low information content. This, together with the separation into two groups, suggests that the predictive value of the spatial positions of the C(α) atoms is not much greater than the sequence alone, aside from their hydrophobicity/hydrophillicity classification.

Original languageEnglish
Pages (from-to)924-938
Number of pages15
JournalJournal of Molecular Biology
Issue number5
StatePublished - 15 Mar 1996
Externally publishedYes


  • Amino acid conservation
  • Amino acid interchanges
  • Geometric hashing
  • Structural motifs
  • Structure comparison

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Molecular Biology


Dive into the research topics of 'Amino acid pair interchanges at spatially conserved locations'. Together they form a unique fingerprint.

Cite this