Abstract:
The Global Range Molecular Matching (GRAMM) methodology is an empirical
approach to smoothing the
macromolecular energy function by changing the range of the atom-atom
potentials. The technique allows to
locate the area of the global minimum of intermolecular energy for
structures of different accuracy. To predict
the structure of a complex, it requires only the atomic coordinates
of the two molecules (no information about
the binding sites is needed). The procedure performs an exhaustive
6-dimensional search through the relative
translations and rotations of the molecules. The molecular pairs may
be: two proteins, a protein and a smaller compound,
two transmembrane helices, etc. GRAMM may be used for high-resolution
molecules (high-resolution docking), for
inaccurate structures, where only the gross structural features are
known, and in cases of large conformational changes
(low-resolution docking). The high-resolution docking is designed for
accurate complex predictions, in case of small
structural inaccuracies. The low-resolution docking is designed for
the prediction of the gross features of a complex,
in case of major structural inaccuracies. It may also be used, for
the accurate structures, to overcome the multiminima
problem, or to reveal the role of large-scale structural factors in
the formation of protein complexes.