DISTANCE GEOMETRY BASED COMPARATIVE MODELING

A distance geometry based protein modelling algorithm is presented whi ch relies on the projection of simple model chain coordinates into Euc lidean spaces with gradually decreasing dimensionality. Fast embedding was achieved by performing separate distance matrix projections on su bsets of the model points. Structural equivalences between the unknown target and related proteins with known structures were deduced either from a mixed sequence/structure multiple alignment or from the output of various fold recognition (threading) approaches. These equivalence s were mapped onto the model as structure-specific conserved C-alpha a tom distances and secondary structure assignments. Additional nonspeci fic distance restraints derived from general stereochemical properties of folded protein chains were used to guide the modelling process. Th e method quickly constructed a large number of low-resolution models w hich could then serve as starting conformations for full-atom refineme nt. Structure predictions for some targets in the 'Asilomar Challenge' (GASPS) are presented to illustrate potential applications of the app roach.