An investigation of phosphopeptide binding to SH2 domain.
A comparative molecular field analysis (CoMFA) was carried out to investigate quantitative structure-activity relationships for SH2-binding phosphopeptides. Two alignment rules were applied in our CoMFA model. The phosphopeptide backbone atoms were used for superposition in alignment I and the backbone atoms of peptide-binding residues of SH2-phosphopeptide complexes were used in alignment II to consider the position of phosphopeptides in SH2-binding sites. The higher correlation and predictivity in alignment II (r(2) value of 0.961 and cross-validated r(2) value of 0.682) suggest that the consideration of peptide-binding position at the binding sites gives rise to better results when the ligand-receptor complex structure is considered. In addition, CoMFA contour and electrostatic maps were well accorded with the experimental results in which the replacement of N-terminal residues with an acetyl group reduced the binding affinity. Therefore, the modification of molecular size and charge of phosphopeptides can be carried out based on these contour maps in order to increase binding affinities.
Lee
Jin Kak
JK
Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, 130-650, Seoul, South Korea.
Moon
Taesung
T
Chi
Myung Whan
MW
Song
Jin-Soo
JS
Choi
Young-Sang
YS
Yoon
Chang No
CN
D000595:Amino Acid Sequence; D001665:Binding Sites; D066298:In Vitro Techniques; D008958:Models, Molecular; D010748:Phosphopeptides / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013816:Thermodynamics; D018909:src Homology Domains
D010748:Phosphopeptides