A protein sequence meta-functional signature for calcium binding residue prediction.
The diversity of characterized protein functions found amongst experimentally interrogated proteins suggests that a vast array of unknown functions remains undiscovered. These protein functions are imparted by specific geometric distributions of amino acid residue chemical moieties, each contributing a functional interaction. We hypothesize that individual residue function contributions are predictable through sequence analytic knowledge based algorithms, and that they can be recombined to understand composite protein function by predicting spatial relation in tertiary structure. We assess the former by training a meta-functional signature algorithm to specifically predict calcium ion binding residues from protein sequence. We estimate the latter by testing for match between predictive contribution of positions in predicted secondary structures and patterns of side chain proximity forced by secondary structure moieties. Specific training for calcium binding results in 83% area under the receiver operator characteristic curve added value over random (AUCoR) and p<10(-300) significance as measured by Kendall's τ in ten fold cross validation for parallel sets of 811 residues in 336 proteins and 696 residues in 299 proteins. Training for generalized function results in 63% AUCoR and p≅10(-221) for the same tests. Including inference of side chain proximity improves predictive ability by 2% AUCoR consistently. The results demonstrate that protein meta-functional signatures can be trained to predict specific protein functions by considering amino acid identity and structural features accessible from sequence, laying the groundwork for composite sequence based function site prediction.
Horst
Jeremy A
JA
Department of Oral Biology, School of Dentistry, University of Washington, 1959 NE Pacific St #357132, Seattle, WA 98195.
Samudrala
Ram
R
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