A robust class of stable proteins in the 2D HPC model

Abstract

The inverse protein folding problem is that of designing an amino acid sequence which has a prescribed native protein fold. This problem arises in drug design where a particular structure is necessary to ensure proper protein-protein interactions. The input to the inverse protein folding problem is a shape and the goal is to design a protein sequence with a unique native fold that closely approximates the input shape. Gupta et al. [10] introduced a design in the 2D HP model of Dill that can be used to approximate any given (2D) shape. They conjectured that the protein sequences of their design are stable but only proved the stability for an infinite class of very basic structures. In [11], we have introduced a refinement of the HP model, in which the cysteine and noncysteine hydrophobic monomers are distinguished and SS-bridges which two cysteines can form are taken into account in the energy function. This model was called the 2D HPC model. In [11], the snake structures in the HPC model were introduced and it was conjectured that they are stable. In this paper, we show that this conjecture is true for a subclass of snake structures. This subclass is robust enough to approximate any given 2D shape, although more coarsely than the general constructible structures proposed in [10]. In the proof we use a semi-automated tool 2DHPSolver developed in [11]. © Springer-Verlag Berlin Heidelberg 2008.