I propose to apply methods of theoretical conformational analysis to the study of the conformation of the collagen molecule and of its packing in fibrils, both in the normal state and when its structure is altered as a result of aging processes or of connective tissue diseases such as elastosis and rheumatic fever. Conformational energy computations will be used to analyze the effects of hydration upon amino acid side chain conformations in the triple helix. New methods of accounting for the solvent contributions to the conformational free energy will be tested on collagen. Constraints on the packing and on the longitudinal alignment of triple helices will be analyzed in terms of noncovalent interactions, including hydration. A similar analysis will be carried out on the collagen-like part of component Clq of the complement system. The computational procedures will be applied also to both nonhelical terminal peptides of collagen. Since these regions of the molecule are essential in cross-linking, their study will contribute to the elucidation of correlations between cross-linking and molecular rearrangements. At the same time, these peptides provide some advantages in the testing of theories for the computation of protein folding. Relationships to be developed between conformational and packing stability on one hand and covalent cross-linking on the other hand will aid the understanding of physico-chemical and physio-logical events in the functioning of normal and of pathologically modified collagen.