# BETASCAN: Probable $$\beta$$-amyloids Identified by Pairwise Probabilistic Analysis

 Title: BETASCAN: Probable $$\beta$$-amyloids Identified by Pairwise Probabilistic Analysis Author: Menke, Matthew; Cowen, Lenore J.; Lindquist, Susan L.; Berger, Bonnie; Bryan, Allen Wayne Note: Order does not necessarily reflect citation order of authors. Citation: Bryan, Allen W., Matthew Menke, Lenore J. Cowen, Susan L. Lindquist, and Bonnie Berger. 2009. BETASCAN: Probable $$\beta$$-amyloids identified by pairwise probabilistic analysis. PLoS Computational Biology 5(3): e1000333. Full Text & Related Files: 2653728.pdf (1.001Mb; PDF) Abstract: Amyloids and prion proteins are clinically and biologically important $$\beta$$-structures, whose supersecondary structures are difficult to determine by standard experimental or computational means. In addition, significant conformational heterogeneity is known or suspected to exist in many amyloid fibrils. Recent work has indicated the utility of pairwise probabilistic statistics in $$\beta$$-structure prediction. We develop here a new strategy for $$\beta$$-structure prediction, emphasizing the determination of $$\beta$$-strands and pairs of $$\beta$$-strands as fundamental units of $$\beta$$-structure. Our program, BETASCAN, calculates likelihood scores for potential $$\beta$$-strands and strand-pairs based on correlations observed in parallel $$\beta$$-sheets. The program then determines the strands and pairs with the greatest local likelihood for all of the sequence's potential $$\beta$$-structures. BETASCAN suggests multiple alternate folding patterns and assigns relative a priori probabilities based solely on amino acid sequence, probability tables, and pre-chosen parameters. The algorithm compares favorably with the results of previous algorithms (BETAPRO, PASTA, SALSA, TANGO, and Zyggregator) in $$\beta$$-structure prediction and amyloid propensity prediction. Accurate prediction is demonstrated for experimentally determined amyloid $$\beta$$-structures, for a set of known $$\beta$$-aggregates, and for the parallel $$\beta$$-strands of $$\beta$$-helices, amyloid-like globular proteins. BETASCAN is able both to detect $$\beta$$-strands with higher sensitivity and to detect the edges of $$\beta$$-strands in a richly $$\beta$$-like sequence. For two proteins (A$$\beta$$ and Het-s), there exist multiple sets of experimental data implying contradictory structures; BETASCAN is able to detect each competing structure as a potential structure variant. The ability to correlate multiple alternate $$\beta$$-structures to experiment opens the possibility of computational investigation of prion strains and structural heterogeneity of amyloid. BETASCAN is publicly accessible on the Web at http://betascan.csail.mit.edu. Published Version: doi:10.1371/journal.pcbi.1000333 Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653728/pdf/ Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10236187 Downloads of this work: