Anomaly Detection-Based Recognition of Near-Native Protein Structures

The three-dimensional structures populated by a protein molecule determine to a great extent its biological activities. The rich information encoded by protein structure on protein function continues to motivate the development of computational approaches for determining functionally-relevant structures. The majority of structures generated in silico are not relevant. Discriminating relevant/native protein structures from non-native ones is an outstanding challenge in computational structural biology. Inherently, this is a recognition problem that can be addressed under the umbrella of machine learning. In this paper, based on the premise that near-native structures are effectively anomalies, we build on the concept of anomaly detection in machine learning. We propose methods that automatically select relevant subsets, as well as methods that select a single structure to offer as prediction. Evaluations are carried out on benchmark datasets and demonstrate that the proposed methods advance the state of the art. The presented results motivate further building on and adapting concepts and techniques from machine learning to improve recognition of near-native structures in protein structure prediction.