From Wikipedia,
the free encyclopedia.
Protein-protein docking
is a field of theoretical
biochemistry aimed at
predicting properties of the
complexes formed by two or
more
proteins. Specifically, for
any given set of proteins, it aims
to answer the following questions:
- If they bind,
- What is the spatial
configuration which they adopt
in their
bound state?
- How strong or weak is
their
interaction?
The field of protein-protein
docking is highly computationally
oriented, and it shares approaches
with
molecular docking. Molecular
docking is sometimes referred to
as small-molecule docking,
to draw a distinction from
protein-protein docking.
Associations between protein and
polynucleotide molecular
structures are widely studied
using similar or identical
approaches to
protein-protein docking,
although if the
nucleotide structure is small
enough, the case may be framed as
a
molecular docking problem.
Generating putative complex
structures
The structures for the
components of the complex must be
available individually; if not,
and their sequence is known, they
may be homology modelled. Then one
of various geometrical techniques
is used to generate possible
structures for the complex itself.
These include:
- A simple series of discrete
translations and rotations of
the components with respect to
each other and to one fixed
component (usually the largest,
to save time).
- A series of molecular
mechanics runs.
If the bond angles, bond
lengths and torsion angles of the
components are not modified at any
stage of complex generation, it is
known as rigid body docking.
It is a subject of debate whether
or not rigid-body docking is
sufficiently good to find most
complexes. When substantial
conformational change occurs
within the components at the time
of complexation, rigid-body
docking is clearly seen to be
inadequate. However exahaustively
accounting for all possible
conformational change is
prohibitively expensive in
computer time; it can be argued
such cases are fundamentally
beyond calculation anyway.
Where the complex is a
homomultimer, each generated
structure may be required to
possess a symmetry axis.
Ranking a generated set of
structures
Heuristic scores are used in
protein-protein docking to compare
the suitability of a set of
putative complexes. Examples are
based on
residue contacts, shape
complementarity of
molecular surfaces, and free
energies estimated using
parameters from
molecular mechanics
force fields developed by
theoretical chemists, such as
CHARMM or
AMBER.
Evolutionary history of
amino-acid sequences of the
associating proteins is also
examined for clues about the
functional site.
Deciding whether or not a
complex actually occurs in nature
and measuring its affinity
A reliable method for affinity
prediction has the potential to
transform biochemistry and cell
biology. This may be considered
the as the ultimate aim of the
protein-protein docking community.
With the scope current methods,
however, affinity predictions
remain a distant prospect.
