Lock - Hierarchical Protein Structure Superposition using...

Info iconThis preview shows pages 1–2. Sign up to view the full content.

View Full Document Right Arrow Icon
Hierarchical Protein Structure Superposition using both Secondary Structure and Atomic Representations Amit P. Singh and Douglas L. Brutlag Section on Medical Informatics and Department of Biochemistry Stanford University, Stanford, CA 94305 apsingh@cmgm.stanford.edu, brutlag@stanford.edu Tel: (415) 723-4025, (415) 723-6593 Fax: (415) 725-6044 Abstract The structural comparison of proteins has become increasingly important as a means to identify protein motifs and fold families. In this paper we present a new algorithm for the comparison of proteins based on a hierarchy of structural representations, from the secondary structure level to the atomic level. Our technique represents α -helices and β -strands as vectors and uses a set of seven scoring functions to compare pairs of vectors from different proteins. The scores obtained are used in a dynamic programming algorithm that finds the best local alignment of the two sets of vectors. The second step in our algorithm is based on the atomic coordinates of the protein structures and improves the initial vector alignment by iteratively minimizing the RMSD between pairs of nearest atoms from the two proteins. We refine the final alignment by determining a core of well aligned atoms and minimizing the RMSD of this core. In a comparison of our method to Holm and Sander’s DALI algorithm, our program was able to detect structural similarity at the same level as DALI. We also performed searches of a representative set of the Protein Data Bank (PDB) using our program and detected structurally similarity between several distantly related proteins. Introduction The number of protein structures in the Brookhaven Protein Data Bank (Bernstein et al., 1977) has been growing rapidly and is currently (as of January, 1997) more than 5,400. The number of known fold families into which these structures can be classified, are, on the other hand, relatively few (Chothia, 1992; Holm and Sander, 1996a; Orengo et al 1993). With the growing number of known unique protein structures, it has become increasingly important to study the levels of structural similarity that exist among these proteins as a means to identify structural motifs and fold families. The comparison of proteins at a structural level is a fundamental step towards the understanding of the folding techniques that are used by biological organisms to construct stable and functional proteins. Structure is also widely believed to be closer to function than sequence, which further emphasizes the importance of studying the three-dimensional relationships within between proteins. In addition, since structure is more highly conserved than sequence, the comparison of protein structures is essential to obtain more accurate estimates of evolutionary distances between proteins protein families.
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 2
This is the end of the preview. Sign up to access the rest of the document.

Page1 / 10

Lock - Hierarchical Protein Structure Superposition using...

This preview shows document pages 1 - 2. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online