Constraint Techniques for Solving the Protein Structure Prediction Problem

Abstract

The protein structure prediction problem is one of the most (if not the most) important problem in computational biology. This problem consists of finding the conformation of a protein (i.e., a sequence of amino-acids) with minimal energy. Because of the complexity of this problem, simplified models like Dill’s HP-lattice model [12] have become a major tool for investigating general properties of protein folding. Even for this simplified model, the structure prediction problem has been shown to be NP-complete [3, 5].

We describe a constraint formulation of the HP-model structure prediction problem, present the basic constraints and search strategy. We then introduce a novel, general technique for excluding geometrical symmetries in constraint programming. To our knowledge, this is the first general and declarative technique for excluding symmetries in constraint programming that can be added to an existing implementation. Finally, we describe a new lower bound on the energy of an HP-protein. Both techniques yield an efficient pruning of the search tree.