A Constraint-Based Approach to Fast and Exact Structure Prediction in Three-Dimensional Protein Models |
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Authors: | Rolf Backofen Sebastian Will |
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Affiliation: | 1. Chair for Bioinformatics, Institute of Computer Science, Friedrich-Schiller-Universit?t Jena, Jena Center for Bioinformatics, Ernst-Abbe-Platz 2, D-07743, Jena, Germany
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Abstract: | Simplified protein models are used for investigating general properties of proteins and principles of protein folding. Furthermore,
they are suited for hierarchical approaches to protein structure prediction. A well known protein model is the HP-model of
Lau and Dill Lau, K. F., & Dill, K. A. (1989)]. A lattice statistical mechanics model of the conformational and sequence
spaces of proteins. Macromolecules, 22, 3986–3997) which models the important aspect of hydrophobicity. One can define the HP-model for various lattices, among
them two-dimensional and three-dimensional ones. Here, we investigate the three-dimensional case. The main motivation for
studying simplified protein models is to be able to predict model structures much more quickly and more accurately than is
possible for real proteins. However, up to now there was a dilemma: the algorithmically tractable, simple protein models can
not model real protein structures with good quality and introduce strong artifacts.
We present a constraint-based method that largely improves this situation. It outperforms all existing approaches for lattice
protein folding in HP-models. This approach is the first one that can be applied to two three-dimensional lattices, namely
the cubic lattice and the face-centered-cubic (FCC) lattice. Moreover, it is the only exact method for the FCC lattice. The ability to use the FCC lattice is a significant
improvement over the cubic lattice. The key to our approach is the ability to compute maximally compact sets of points (used
as hydrophobic cores), which we accomplish for the first time for the FCC lattice. |
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Keywords: | Protein structure prediction HP-model Face-centered cubic lattice Constraint programming |
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