Splitting statistical potentials into meaningful scoring functions: testing the prediction of near-native structures from decoy conformations.

BMC Structural Biology
Patrick Aloy, Baldo Oliva

Abstract

Recent advances on high-throughput technologies have produced a vast amount of protein sequences, while the number of high-resolution structures has seen a limited increase. This has impelled the production of many strategies to built protein structures from its sequence, generating a considerable amount of alternative models. The selection of the closest model to the native conformation has thus become crucial for structure prediction. Several methods have been developed to score protein models by energies, knowledge-based potentials and combination of both. Here, we present and demonstrate a theory to split the knowledge-based potentials in scoring terms biologically meaningful and to combine them in new scores to predict near-native structures. Our strategy allows circumventing the problem of defining the reference state. In this approach we give the proof for a simple and linear application that can be further improved by optimizing the combination of Zscores. Using the simplest composite score (ZECbeta) we obtained predictions similar to state-of-the-art methods. Besides, our approach has the advantage of identifying the most relevant terms involved in the stability of the protein structure. Finally, we also use the compos...Continue Reading

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Citations

Nov 18, 2010·Journal of Molecular Modeling·Núria Cerdà-CostaSandra Villegas
Mar 25, 2011·Protein Science : a Publication of the Protein Society·Elisenda FeliuBaldo Oliva
Aug 17, 2020·Protein Science : a Publication of the Protein Society·Alberto MeseguerBaldo Oliva

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Methods Mentioned

BETA
protein folding
X-ray

Software Mentioned

lmds
DOPE
FUGUE
MODEL
TOPITS
FoldX
LOOPP
QMEAN
PCONS
MODELLER

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