Prediction of Protein-Protein Binding Interfaces - Identification of Ligand Binding Site and Protein-Protein Interaction Area - page 127

The “fuzzy oil drop” package attempts to link the final state of the complex with
the mechanisms which govern the folding process. We assume that an undisturbed
molecule folding in an aqueous environment generates a regular hydrophobic core,
as is evident in fast-folding (Roterman et al. 2011 a, b) and antifreeze proteins
(Banach et al. 2012 ). The presence of an external ligand (Bryliński et al. 2007a , b ) ,
a partner molecule or a membrane (Zobnina and Roterman 2009 ) deforms the core
of the emerging protein in a way which ensures its specificity. Note that even though
fully folded proteins may encounter a wide variety of potential ligands in their envi-
ronment, they are usually highly specific with regard to the molecules they bind
with. Some researchers even postulate that the presence of a ligand is an essential
factor in the polypeptide chain folding process (Brylinski et al. 2006, 2007a ) .
As highlighted in our analysis, the “fuzzy oil drop” model is capable of acknowl-
edging such factors and explains how proteins are conditioned to perform their
intended biological role. This is especially important in enzymes, where localized
deformations of the hydrophobic core seem to correspond to active sites of hydro-
lases (Prymula et al. 2011 ) .
Genomics-scale analysis of protein complexes suggests that, when it comes to
determining the biological profiles of proteins, complexation is frequently as impor-
tant as interaction with ligands. A noteworthy presentation of current progress in
studying protein complexation mechanisms can be found in Fleishman et al.
( 2011 )
Acknowledgements The presented research was carried out in 1995-2011 and funded by a series
of grants from the Jagiellonian University Medical College. The Academic Computing Center
CYFRONET AGH Krakow provided computational support. We would like to express our grati-
tude to Piotr Nowakowski of CYFRONET AGH for valuable editorial remarks. Technical support
provided by Anna Zaremba-Śmietańska is also gratefully acknowledged.
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