Tools and Databases to Analyze Protein Flexibility; Approaches to Mapping Implied Features onto Sequences

This chapter describes the way protein flexibility can be analyzed statistically in a database. The database of macromolecular movements, which is accessible over the Internet, organizes a few hundred well-characterized motions on the basis of size and then packing, with the involvement of a well-packed interface in the motion being a key classifying feature. The chapter describes the computational tools employed in the database analysis—namely, (1) structure comparison, which is useful to align and superpose different conformations, (2) adiabatic mapping interpolation, which is implemented on a large scale by the morph server, provides movie-like pathways between two superposed conformations, and in the process, generates many standardized statistics, (3) normal mode analysis, which provides readily interpretable information about the flexibility of a single conformation, and (4) Voronoi volume calculations, which provide a rigorous basis for characterizing packing. The chapter also explains the way structural features in the motions database can be related to sequence, an important part of the overall process of transferring annotation to uncharacterized genomic data. This allows determination of a sequence-propensity scale for amino acids to be in linkers in general or flexible hinges in particular.