Global characterization of protein secondary structures. Analysis of computer-modeled protein unfolding

Analyses of structural and molecular shape changes undergone by a protein during an unfolding process are presented. The procedure, based on a spherical shape map method, provides a topological description of a three-dimensional macromolecular structure. Local properties of the backbone are used to derive a global characterization of its fold. A spherical shape map of backbone crossings is associated with a given macromolecular conformation. The map is built by classifying each point on the sphere according to the crossing pattern obtained when the backbone is observed along a direction defined by the center of the sphere and the chosen point. The surface of the sphere can be divided in equivalence classes. All the points within a given class correspond to directions from which the backbone has the same overcrossing pattern. Automatic computation and display of these equivalence classes is discussed, as is the implementation of the technique on a computer graphics workstation. The graphical manipulation simplifies the analysis of these maps when following a change in the conformation of the backbone. The procedure is illustrated with the results of a molecular dynamics computer simulation of the unfolding of the bacteriophage T4 glutaredoxin protein (in the form of its polyglycine model). The method gives a novel description of the differential structural stability for the characteristic secondary structural elements (alpha-helices and beta-sheets) present in the protein. Recognition of the persistence of structural elements over the simulation time is performed in an unbiased manner.