By Topic

Reduced False Positives in PDZ Binding Prediction Using Sequence and Structural Descriptors

Sign In

Cookies must be enabled to login.After enabling cookies , please use refresh or reload or ctrl+f5 on the browser for the login options.

Formats Non-Member Member
$33 $13
Learn how you can qualify for the best price for this item!
Become an IEEE Member or Subscribe to
IEEE Xplore for exclusive pricing!
close button

puzzle piece

IEEE membership options for an individual and IEEE Xplore subscriptions for an organization offer the most affordable access to essential journal articles, conference papers, standards, eBooks, and eLearning courses.

Learn more about:

IEEE membership

IEEE Xplore subscriptions

4 Author(s)

Identifying the binding partners of proteins is a problem of fundamental importance in computational biology. The PDZ is one of the most common and well-studied protein binding domains, hence it is a perfect model system for designing protein binding predictors. The standard approach to identifying the binding partners of PDZ domains uses multiple sequence alignments to infer the set of contact residues that are used in a predictive model. We expand on the sequence alignment approach by incorporating structural information to generate descriptors of the binding site geometry. Furthermore, we generate a real-value score for binary predictions by applying a filter based on models that predict the probability distributions of contact residues at each of the canonical PDZ ligand binding positions. Under training cross validation, our model produced an order of magnitude more predictions at a false positive proportion (FPP) of 10 percent than our benchmark model chosen from the literature. Evaluated using an independent cross validation, with computationally predicted structures, our model was able to make five times as many predictions as the benchmark model, with a Matthews' correlation coefficient (MCC) of 0.33. In addition, our model achieved a false positive proportion of 0.14, while the benchmark model had a 0.25 false positive proportion.

Published in:

IEEE/ACM Transactions on Computational Biology and Bioinformatics  (Volume:9 ,  Issue: 5 )