6 Advantages and Disadvantages of Protein–Protein Docking
The examples of PPD studies described above show that the
method can be used for various purposes. Nowadays, protein–pro-
tein docking is the most useful technique for modeling protein
complexes by combining several advantages: (a) It is easy to use;
(b) it returns results quickly and does not require significant com-
puter resources (particularly when compared to MD techniques);
and (c) it provides a structural model for the complexes (unlike
sequence based methods that only highlight interface-forming
residues) [16]. As such, it can very quickly provide some clues or
initial hypotheses for further investigation. It can also provide
several complexes for further testing. It is clearly an advantage
over the more accurate, but significantly slower experimental meth-
ods like X-ray crystallography. However, it has to be stressed that
drawbacks of the method, i.e., difficulty of proper identification of
interaction interface, limited possibility of side chain and backbone
flexibility consideration (seeNote 2) and uncertainty of scoring (see
Note 3), make the method more suitable as support for experimen-
tal methods or to be used together with molecular dynamics simu-
lations rather than an independent experimental tool. Therefore,
while application of PPD can significantly reduce the time and cost
of a mutagenetic study, any protein–protein docking results should
be treated with a limited trust, and can be considered conclusive
only if validated.7 Summary and Perspective
A number of protein–protein docking algorithms are now available
to address the problem of protein–protein interactions and to
provide 3D structures of protein complexes necessary for applica-
tion of structure-based design techniques. A considerable progress
has been achieved regarding the development of scoring functions
based on physical interactions, shape complementarity, geometry,
interface water molecules, and the accommodation of protein flexi-
bility [3]. The capabilities of protein–protein docking software can
be improved as it can be concluded from CAPRI experiments. The
importance of protein–protein docking approaches can increase in
future due to the attractive possibility of designing protein–protein
interaction modulators. On the other hand, along with the avail-
ability of advanced molecular dynamics techniques and progress in
computational power and resources, the application of protein–-
protein docking might become complementary to molecular
dynamics simulations.Protein-Protein Docking 299