A Descriptive Analysis Of Populations Of Three-Dimensional Structures Calculated From Primary Sequences Of Proteins By Osiris

Among different ab initio approaches to calculate 3D-structures of proteins out
of primary sequences, a few are using restricted dihedral spaces and empirical
equations of energy as is OSIRIS. All those approaches were calibrated on a few
proteins or fragments of proteins. To optimize the calculation over a larger
diversity of structures, we need first to define for each sequence what are good
conditions of calculations in order to choose a consensus procedure fitting most
3D-structures best. This requires objective classification of calculated
3D-structures. In this work, populations of avian and bovine pancreatic
polypeptides (APP, BPP) and of calcium-binding protein (CaBP) are obtained by
varying the rate of the angular dynamics of the second step of OSIRIS. Then,
3D-structures are clustered using a nonhierarchical method, SICLA, using rmsd as
a distance parameter. A good clustering was obtained for four subpopulations of
APP, BPP and CaBP. Each subpopulation was characterized by its barycenter,
relative frequency and dispersion. For the three alpha-helix proteins, after the
step 1 of OSIRIS, most secondary structures were correct but molecules have a few
atomic contacts. Step 2, i.e., the angular dynamics, resolves those atomic
contacts and clustering demonstrates that it generates subpopulations of
topological conformers as the barycenter topologies show.