Significant improvement of the pairwise contact energies for proteins

Recent attempts to construct a global pairwise contact energy function of amino acids for proteins have not succeeded in stabilizing the native states of many proteins simultaneously. In this paper, we show that the systematic inclusion of the local environments of the amino acids in the design of such a function leads to success in designing a global protein energy function. We design and construct two kinds of pairwise contact energy functions by considering either the secondary structures or the hydrophobicities (solvation) of the amino acids and by using perceptron learning and protein threading. These can stabilize all native states of 1,006 proteins simultaneously with 30% homology. When these two energy functions are subject to a threading test on 382 new distinct proteins, the energy function with the secondary structure information can stabilize 300 (78.5%) proteins out of 382 proteins whereas the energy function with the hydrophobicity information can stabilize 367 (96%) proteins. This illustrates the critical role played by the hydrophobicity of amino acids in stabilizing the essential structures of proteins. Both the hydrophobicity and the secondary structure are important to assess the protein structure, and the impact of the hydrophobicity is elucidated in this work through the process of designing global pairwise contact energies for proteins. We expect that the simultaneous inclusion of the hydrophobicity, the secondary structure, and other local environments, such as the polarity and the structures of neighboring of amino acids, will enable us to design better protein energy functions by using perceptron learning and protein threading.