HOMOLOGY MODELING OF THE ABL-SH3 DOMAIN

A tertiary structure model of the Ab1-SH3 domain is predicted by using homology modeling techniques coupled to molecular dynamics simulation s. Two template proteins were used, Fyn-SH3 and Spc-SH3. The refined m odel was extensively checked for errors using criteria based on stereo chemistry, packing, solvation free-energy, accessible surface areas, a nd contact analyses. The different checking methods do not totally agr ee, as each one evaluates a different characteristic of protein struct ures. Several zones of the protein are more susceptible to incorporati ng errors. These include residues 13, 15, 35, 39, 45, 46, 50, and 60. An interesting finding is that the measurement of the C alpha chiralit y correlated well with the rest of the criteria, suggesting that this parameter might be a good indicator of correct local conformation. Dev iations of more than 4 degrees may be indicative of poor local structu re. (C) 1994 Wiley-Liss, Inc.