The article presents a database of homology-derived protein structures (HSSP) and discusses the structural significance of sequence alignment. The authors aim to expand the known protein structure database by using sequence homology, which is more extensive than the current structure database. They quantify the relationship between sequence similarity, structure similarity, and alignment length through an exhaustive survey of known structures. A homology threshold curve is derived as a function of alignment length, which helps determine when sequence similarity implies structural homology. The HSSP database is created by aligning all homologous sequences to each known structure, providing information on secondary structure, sequence variability, and sequence profile. This database increases the number of known structures by a factor of five, to over 1800. The results have applications in assessing structural significance of sequence matches, deriving structure prediction preferences, and elucidating the role of conserved residues. The authors also discuss the limitations of the database, the accuracy of homology-derived structures, and the use of the HSSP database in future research. The database is available for free distribution and includes information on sequence variation, structural homology, and sequence profiles. The authors conclude that the HSSP database is a valuable resource for studying protein structure and evolution.The article presents a database of homology-derived protein structures (HSSP) and discusses the structural significance of sequence alignment. The authors aim to expand the known protein structure database by using sequence homology, which is more extensive than the current structure database. They quantify the relationship between sequence similarity, structure similarity, and alignment length through an exhaustive survey of known structures. A homology threshold curve is derived as a function of alignment length, which helps determine when sequence similarity implies structural homology. The HSSP database is created by aligning all homologous sequences to each known structure, providing information on secondary structure, sequence variability, and sequence profile. This database increases the number of known structures by a factor of five, to over 1800. The results have applications in assessing structural significance of sequence matches, deriving structure prediction preferences, and elucidating the role of conserved residues. The authors also discuss the limitations of the database, the accuracy of homology-derived structures, and the use of the HSSP database in future research. The database is available for free distribution and includes information on sequence variation, structural homology, and sequence profiles. The authors conclude that the HSSP database is a valuable resource for studying protein structure and evolution.