Automated protein structure annotation


Annotation & Function


Novel methods have been developed that automatically examine protein structures and extract structural functional information. Functional analysis of all PSI-1 and PSI-2 NYSGXRC structures, including tabulations of structure comparison and output from Dali, CE, and SURFNET, are available at


The Albert Einstein College of Medicine bioinformatics group is working on the development of novel methods to automatically examine protein structures and extract functional information that cannot be inferred from sequence(s) alone. A pipeline has been established for structure-based functional annotation of proteins. Newly deposited experimental structures are compared to all known folds using Dali (Holm and Rosenström, 2010), CE (Shindyalov and Bourne, 1998), and SURFNET (Laskowski RA, 1995) algorithms. These algorithms have been implemented in-house, providing access to frequently updated reference databases and faster processing over internet-based alternatives. If functionally annotated related structures are found, these annotations are used to characterize the target protein. In the case that related structures are found but are not described functionally, a newly developed Spheres algorithm (Fajardo, Levine, and Fiser, in preparation) is used to identify structurally invariant residues in these models. The Spheres algorithm is an iterative superposition method that dissects protein molecules in small, local units, produces an all-to-all superposition of all of them, then structurally and sequentially scores and identifies the most similar ones. These similar substructures typically reconstruct the general environment of the functional sites. The identified residues are then further filtered by an implementation of a graph theory-based 'closeness' algorithm that identifies networks of highly connected residues (Amitai et al., 2004). Functional analysis of all NYSGXRC structures, including tabulations of structure comparison and output from Dali, CE, and SURFNET, are available at


Holm L, Rosenström P (2010) Dali server: conservation mapping in 3D. Nucl. Acids Res. 38, W545-549. PubMed ID:20457744 | PMC Link

Shindyalov IN, Bourne PE. "Protein structure alignment by incremental combinatorial extension (CE) of the optimal path." Protein Eng. 11, 739-47 (1998). PubMed ID:9796821

Laskowski R A (1995). SURFNET: A program for visualizing molecular surfaces, cavities and intermolecular interactions. J. Mol. Graph., 13, 323-330. PubMed ID:8603061

Amitai G, Shemesh A, Sitbon E, Shklar M, Netanely D, Venger I, Pietrokovski S. "Network analysis of protein structures identifies functional residues." J Mol Biol. 344, 1135-46 (2004). PubMed ID:15544817


Andras Fiser, PhD;

New York Structural Genomics Research Consortium


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Last edited:Wed 25 May 2011 - 5 years, 10 months ago