Lattice protein
Encyclopedia
Lattice proteins are highly simplified computer models of protein
s which are used to investigate protein folding
.
Because proteins are such large molecules
, there are severe computational limits on the simulated timescales of their behaviour when modeled in all-atom detail. The millisecond
regime for all-atom simulations was not reached until 2010, and it is still not possible to fold all real proteins on a computer. Lattice proteins, however, are simplified in two ways: the amino acid
s are modelled as single "beads" rather than modeling every atom, and the beads are restricted to a rigid (usually cubic) lattice. This simplification allows them to reach their energy minima in a time quick enough to be simulated in full.
Lattice proteins are made to resemble real proteins by introducing an energy function, a set of conditions which specify the interaction energy
between neighbouring beads, usually those occupying adjacent lattice sites. The energy function mimics the interactions between amino acids in real proteins, which include steric, hydrophobic
and hydrogen bonding effects. The beads are divided into types, and the energy function specifies the interactions depending on the bead type, just as different types of amino acids interact differently. One of the most popular lattice models, the HP model, features just two bead types—hydrophobic (H) and polar
(P)—and mimics the hydrophobic effect
by specifying a negative (i.e. favourable) interaction between H beads.
For any sequence in any particular structure, an energy can be rapidly calculated from the energy function. For the simple HP model, this is simply an enumeration of all the contacts between H residues that are adjacent in the structure but not in the chain. 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. 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 diagram
s 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. In particular, lattice models have been used to investigate the energy landscape
s of proteins, i.e. the variation of their internal free energy
as a function of conformation.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s which are used to investigate protein folding
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
.
Because proteins are such large molecules
Macromolecule
A macromolecule is a very large molecule commonly created by some form of polymerization. In biochemistry, the term is applied to the four conventional biopolymers , as well as non-polymeric molecules with large molecular mass such as macrocycles...
, there are severe computational limits on the simulated timescales of their behaviour when modeled in all-atom detail. The millisecond
Millisecond
A millisecond is a thousandth of a second.10 milliseconds are called a centisecond....
regime for all-atom simulations was not reached until 2010, and it is still not possible to fold all real proteins on a computer. Lattice proteins, however, are simplified in two ways: the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s are modelled as single "beads" rather than modeling every atom, and the beads are restricted to a rigid (usually cubic) lattice. This simplification allows them to reach their energy minima in a time quick enough to be simulated in full.
Lattice proteins are made to resemble real proteins by introducing an energy function, a set of conditions which specify the interaction energy
Interaction energy
In physics, interaction energy is the contribution to the total energy that is caused by an interaction between the objects being considered.The interaction energy usually depends on the relative position of the objects...
between neighbouring beads, usually those occupying adjacent lattice sites. The energy function mimics the interactions between amino acids in real proteins, which include steric, hydrophobic
Hydrophobic effect
The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in aqueous solution and exclude water molecules. The name, literally meaning "water-fearing," describes the segregation and apparent repulsion between water and nonpolar substances...
and hydrogen bonding effects. The beads are divided into types, and the energy function specifies the interactions depending on the bead type, just as different types of amino acids interact differently. One of the most popular lattice models, the HP model, features just two bead types—hydrophobic (H) and polar
Dipole
In physics, there are several kinds of dipoles:*An electric dipole is a separation of positive and negative charges. The simplest example of this is a pair of electric charges of equal magnitude but opposite sign, separated by some distance. A permanent electric dipole is called an electret.*A...
(P)—and mimics the hydrophobic effect
Hydrophobic effect
The hydrophobic effect is the observed tendency of nonpolar substances to aggregate in aqueous solution and exclude water molecules. The name, literally meaning "water-fearing," describes the segregation and apparent repulsion between water and nonpolar substances...
by specifying a negative (i.e. favourable) interaction between H beads.
For any sequence in any particular structure, an energy can be rapidly calculated from the energy function. For the simple HP model, this is simply an enumeration of all the contacts between H residues that are adjacent in the structure but not in the chain. 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. This is the energetic ground state, or native state
Native state
In biochemistry, the native state of a protein is its operative or functional form. While all protein molecules begin as simple unbranched chains of amino acids, once completed they assume highly specific three-dimensional shapes; that ultimate shape, known as tertiary structure, is the folded...
. 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 diagram
Phase diagram
A phase diagram in physical chemistry, engineering, mineralogy, and materials science is a type of chart used to show conditions at which thermodynamically distinct phases can occur at equilibrium...
s of different substances can be scaled onto one another (the theorem of corresponding states
Theorem of corresponding states
According to van der Waals, the theorem of corresponding states indicates that all fluids, when compared at the same reduced temperature and reduced pressure, have approximately the same compressibility factor and all deviate from ideal gas behavior to about the same degree.Material constants that...
).
By varying the energy function and the bead sequence of the chain (the primary structure), effects on the native state structure and the kinetics
Chemical kinetics
Chemical kinetics, also known as reaction kinetics, is the study of rates of chemical processes. Chemical kinetics includes investigations of how different experimental conditions can influence the speed of a chemical reaction and yield information about the reaction's mechanism and transition...
of folding can be explored, and this may provide insights into the folding of real proteins. In particular, lattice models have been used to investigate the energy landscape
Energy landscape
In physics, an energy landscape is a mapping of all possible conformations of a molecular entity, or the spatial positions of interacting molecules in a system, and their corresponding energy levels, typically Gibbs free energy, on a two- or three-dimensional Cartesian coordinate system.In...
s of proteins, i.e. the variation of their internal free energy
Thermodynamic free energy
The thermodynamic free energy is the amount of work that a thermodynamic system can perform. The concept is useful in the thermodynamics of chemical or thermal processes in engineering and science. The free energy is the internal energy of a system less the amount of energy that cannot be used to...
as a function of conformation.