Conformational Studies On Globular Proteins : An Alpha-Carbon Based Algorithm For Identifying Secondary Structures

Abstract

The foregoing sections of this chapter provided an introduction to the conformational study of polypeptide chains and described the general features of the structure of globular proteins. The conformation of the side chains has not been discussed here, though detailed studies exist (Janin et al., 1978; Warme and Morgan, 1978; Crippen and Kuntz, 1978). Two other important topics which are related to the structure of globular proteins are protein folding (the study of the forces and pathways involved in folding the protein molecule into its unique three-dimensional shape) and the methods of prediction of secondary structures from the primary structure. These fall outside the scope of the thesis.

The application of the algorithm to the C-proteins has served the dual purpose of providing complete lists of secondary structures for all proteins whose structures are known. That the algorithm developed in the thesis can quickly spot some types of geometrical/stereochemical problems in the protein structure can prove helpful in arriving at an accurate structure. This check may be applied at any stage in the X-ray study of the protein, but will be most useful in the early stages.

It may be pointed out here that the errors in the final set of coordinates may be due to several reasons which include the following two: (i) Errors in the preliminary set of coordinates obtained from the model. (ii) Errors in transforming this into the final set that is available from the PDB.

The approaches described in this chapter can only point to possible errors in the coordinates and cannot trace their origin.

The application to cyclic and linear oligopeptides has shown that the algorithm can be useful in the study of their conformation, though in a limited way. What is described in this Appendix is a preliminary step in the study of the solvent accessibility of the secondary structures. It will be interesting and fruitful to compute the ASA (Accessible Surface Area) of isolated helices, -sheets, and -bends, and compare them with the values obtained for these structures when they are parts of proteins in the folded state. Such a study will give information regarding the general tendency of each type of secondary structure to bury itself or remain exposed during the folding of the protein. This could enhance our understanding of the process of protein folding.