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. 2011 Dec:1062-1067.
doi: 10.1109/ICDM.2011.88.

Learning Protein Folding Energy Functions

Wei Guan  1 , Arkadas Ozakin  2 , Alexander Gray  1 , Jose Borreguero  3 , Shashi Pandit  3 , Anna Jagielska  3 , Liliana Wroblewska  3 , Jeffrey Skolnick  3
Affiliations

Learning Protein Folding Energy Functions

Wei Guan et al. Proc IEEE Int Conf Data Min. 2011 Dec.

Abstract

A critical open problem in ab initio protein folding is protein energy function design, which pertains to defining the energy of protein conformations in a way that makes folding most efficient and reliable. In this paper, we address this issue as a weight optimization problem and utilize a machine learning approach, learning-to-rank, to solve this problem. We investigate the ranking-via-classification approach, especially the RankingSVM method and compare it with the state-of-the-art approach to the problem using the MINUIT optimization package. To maintain the physicality of the results, we impose non-negativity constraints on the weights. For this we develop two efficient non-negative support vector machine (NNSVM) methods, derived from L2-norm SVM and L1-norm SVMs, respectively. We demonstrate an energy function which maintains the correct ordering with respect to structure dissimilarity to the native state more often, is more efficient and reliable for learning on large protein sets, and is qualitatively superior to the current state-of-the-art energy function.

Keywords: ab initio protein folding; energy function; learning-to-rank; non-negativity constrained SVM optimization; support vector machine.

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Figures

Figure 1
Figure 1
Energy versus Structural Dissimilarity Plot: each dot represents a non-native conformation, and the red square represents the native structure
Figure 2
Figure 2
Error Plot of the Performance of the Learned Energy Functions
Figure 3
Figure 3
NNSVM Optimization Method Comparison
See this image and copyright information in PMC

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