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MODELLER is a computer program that models three-dimensional structures of proteins and their assemblies by satisfaction of spatial restraints.
MODELLER is most frequently used for homology or comparative protein structure modeling: The user provides an alignment of a sequence to be modeled with known related structures and MODELLER will automatically calculate a model with all non-hydrogen atoms (these structures are often homologs, but certainly don't have to be, hence the term “comparative” modeling).
More generally, the input to the program are restraints on the spatial structure of the amino acid sequence(s) and ligands to be modeled. The output is a 3D structure that satisfies these restraints as well as possible. Restraints can in principle be derived from a number of different sources. These include related protein structures (comparative modeling), NMR experiments (NMR refinement), rules of secondary structure packing (combinatorial modeling), cross-linking experiments, fluorescence spectroscopy, image reconstruction in electron microscopy, site-directed mutagenesis, intuition, residue-residue and atom-atom potentials of mean force, etc. The restraints can operate on distances, angles, dihedral angles, pairs of dihedral angles and some other spatial features defined by atoms or pseudo atoms. Presently, MODELLER automatically derives the restraints only from the known related structures and their alignment with the target sequence.
A 3D model is obtained by optimization of a molecular probability density function (pdf). The molecular pdf for comparative modeling is optimized with the variable target function procedure in Cartesian space that employs methods of conjugate gradients and molecular dynamics with simulated annealing.
MODELLER can also perform multiple comparison of protein sequences and/or structures, clustering of proteins, and searching of sequence databases. The program is used with a scripting language and does not include any graphics. It is written in standard FORTRAN 90 and will run on UNIX, Windows, or Mac computers.