Lattice proteins are highly simplified models of protein-like heteropolymer chains on lattice conformational space which are used to investigate protein folding. Simplification in lattice proteins is twofold: each whole residue (amino acid) is modeled as a single "bead" or "point" of a finite set of types (usually only two), and each residue is restricted to be placed on vertices of a (usually cubic) lattice. and it is still not possible to fold all real proteins on a computer. Simplification significantly reduces the computational effort in handling the model, although even in this simplified scenario the protein folding problem is NP-complete.
Overview
Different versions of lattice proteins may adopt different types of lattice (typically square and triangular ones), in two or three dimensions, but it has been shown that generic lattices can be used and handled via a uniform approach.
Lattice proteins are made to resemble real proteins by introducing an energy function, a set of conditions which specify the interaction energy between beads occupying adjacent lattice sites. features just two bead types—hydrophobic (H) and polar (P)—and mimics the hydrophobic effect by specifying a favorable interaction between H beads. Most researchers consider a lattice protein sequence protein-like only if it possesses a single structure with an energetic state lower than in any other structure, although there are exceptions that consider ensembles of possible folded states. This is the energetic ground state, or native state. The relative positions of the beads in the native state constitute the lattice protein's tertiary structure. Lattice proteins do not have genuine secondary structure; however, some researchers have claimed that they can be extrapolated onto real protein structures which do include secondary structure, by appealing to the same law by which the phase diagrams of different substances can be scaled onto one another (the theorem of corresponding states).
By varying the energy function and the bead sequence of the chain (the primary structure), effects on the native state structure and the kinetics of folding can be explored, and this may provide insights into the folding of real proteins. Some of the examples include study of folding processes in lattice proteins that have been discussed to resemble the two-phase folding kinetics in proteins. Lattice protein was shown to have quickly collapsed into compact state and followed by slow subsequent structure rearrangement into native state. Attempts to resolve Levinthal paradox in protein folding are another efforts made in the field. As an example, study conducted by Fiebig and Dill examined searching method involving constraints in forming residue contacts in lattice protein to provide insights to the question of how a protein finds its native structure without global exhaustive searching. Lattice protein models have also been used to investigate the energy landscapes of proteins, i.e. the variation of their internal free energy as a function of conformation.
Lattices
A lattice is a set of orderly points that are connected by "edges". Hexagonal lattices with diagonals have also been suggested as a way to combat the parity problem. It is considered to be the paradigmatic lattice protein model.
Problems and alternative models
The simplicity of the hydrophobic-polar model has caused it to have several problems that people have attempted to correct with alternative lattice protein models. adding additional parameters to reduce the number of low energy conformations and allowing for more realistic protein simulations.
Another issue with lattice models is that they generally don't take into account the space taken up by amino acid side chains, instead considering only the α-carbon.