Long-range information and physicality constraints improve predicted protein contact maps

Protein topology representations such as residue contact maps are an important intermediate step towards ab initio prediction of protein structure, but the problem of predicting reliable contact maps is far from solved. One of the main pitfalls of existing contact map predictors is that they generally predict unphysical maps, i.e. maps that cannot be embedded into three-dimensional structures or, at best, violate a number of basic constraints observed in real protein structures, such as the maximum number of contacts for a residue. Here, we focus on the problem of learning to predict more "physical" contact maps. We do so by first predicting contact maps through a traditional system (XXStout), and then filtering these maps by an ensemble of artificial neural networks. The filter is provided as input not only the bare predicted map, but also a number of global or long-range features extracted from it. In a rigorous cross-validation test, we show that the filter greatly improves the predicted maps it is input. CASP7 results, on which we report here, corroborate this finding. Importantly, since the approach we present here is fully modular, it may be beneficial to any other ab initio contact map predictor.