Background: Cell adhesion involves interactions of integrins and extracellular proteins, often facilitated by the RGD motif. Only presence of the RGD in a sequence of a protein may be not sufficient for the biological activity (binding to an integrin) and additional biochemical and/or structural studies are essential.
Material/Methods: Structural criteria that would allow identification biologically active RGD-sites on the base of a spatial structure may assist analysis of function of a protein in the cell. For the first time, computational analysis of RGD-sites in a large non-redundant set of protein structures was done.
Results: Out of 3819 protein chains sequences of about 100 contained RGDs. Analysis of the structures of the RGD-’native’ proteins has allowed establishing main determinants of the biologically
active conformations of the RGD sites: surface accessibility of the whole RGD-sequence and the secondary structure. The criteria, applied to the remaining proteins of the set, identify 23 proteins (~25%) with potentially active RGD-sites. The results strongly suggest that RGD has
a high propensity for being involved in protein-protein interactions and this may explain occurrence of RGDs in intracellular proteins.
Results of the analysis suggest (in some cases, confirm) novel integrin-related activities for 7 membrane/extracellular proteins, as well as confirm RGD-facilitated cell attachment for 5 viral
proteins.
Conclusions: Only presence of RGD in a sequence is not sufficient to propose biological activity of this site. The results also suggest that the method can be used on large scale: for example, for identifying
potential integrin-interacting proteins in an animal genome.

Keywords: Amino Acid Sequence, Computational Biology, Disintegrins - chemistry, Integrins - metabolism, Models, Molecular, Molecular Sequence Data, Oligopeptides - chemistry, Oligopeptides - genetics, Protein Conformation, Proteins - chemistry, Proteins - genetics, Receptors, Immunologic - chemistry