Evaluation of protein fold comparison servers

• Published in: Proteins, structure, function, and bioinformatics Vol. 54; no. 2; pp. 260 - 270
• Main Authors: Novotny, Marian, Madsen, Dennis, Kleywegt, Gerard J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-02-2004
• Subjects: Comparative Study; Computational Biology; Cyclophilins - chemistry; Cyclophilins - classification; Cyclophilins - metabolism; Cyclophilins/chemistry/classification/metabolism; Databases, Protein; fold classification; Information Storage and Retrieval; Internet; protein fold; Protein Folding; protein structure; Protein Structure, Tertiary; Proteins - chemistry; Proteins - classification; Proteins - metabolism; Proteins/chemistry/classification/metabolism; Software; structural bioinformatics; structure comparison; structure superposition; Structure-Activity Relationship; User-Computer Interface; Research Support; Databases; Protein Structure; Non-U.S. Gov't; Tertiary; Protein
• ISSN: 0887-3585; 1097-0134; 1097-0134
• DOI: 10.1002/prot.10553

When a new protein structure has been determined, comparison with the database of known structures enables classification of its fold as new or belonging to a known class of proteins. This in turn may provide clues about the function of the protein. A large number of fold comparison programs have been developed, but they have never been subjected to a comprehensive and critical comparative analysis. Here we describe an evaluation of 11 publicly available, Web‐based servers for automatic fold comparison. Both their functionality (e.g., user interface, presentation, and annotation of results) and their performance (i.e., how well established structural similarities are recognized) were assessed. The servers were subjected to a battery of performance tests covering a broad spectrum of folds as well as special cases, such as multidomain proteins, Cα‐only models, new folds, and NMR‐based models. The CATH structural classification system was used as a reference. These tests revealed the strong and weak sides of each server. On the whole, CE, DALI, MATRAS, and VAST showed the best performance, but none of the servers achieved a 100% success rate. Where no structurally similar proteins are found by any individual server, it is recommended to try one or two other servers before any conclusions concerning the novelty of a fold are put on paper. Proteins 2004. © 2003 Wiley‐Liss, Inc.