HPmodel

HPmodel, short for hydrophobic-polar model, is a simplified lattice model used to study the basic principles of protein folding. The model was introduced in 1989 by Lau and Dill and has since become a standard toy model in computational biology. In the HP model, a protein is represented as a self-avoiding walk on a regular lattice, typically two- or three-dimensional. Each monomer is labeled as hydrophobic (H) or polar (P). Consecutive monomers occupy adjacent lattice sites, while non-consecutive hydrophobic contacts that occur on neighboring sites contribute to the energy of the conformation.

The energy is usually taken as E = - (number of non-bonded HH contacts). Thus stable structures minimize energy by maximizing HH contacts, which correspond to the formation of a hydrophobic core. The model supports both two-dimensional and three-dimensional lattices, with the lattice choice influencing the search space and folding behavior.

Variants and computational aspects: Most studies use a 2D square lattice; some extend to 3D cubic lattices or other lattices. Finding the ground state is computationally challenging and is NP-hard for many lattice formulations. Exact enumeration is feasible only for short chains; for longer sequences researchers rely on Monte Carlo methods, simulated annealing, or other heuristics.

Significance and limitations: The HP model serves as a conceptual framework for exploring how hydrophobicity drives folding and for testing algorithms. It is a highly simplified representation and omits many features of real proteins, such as diverse amino-acid types, off-lattice geometry, side-chain interactions, and solvent effects. As a result, results from HP-model studies are qualitative rather than predictive of real protein structures.