  The protein-protein interactions (PPIs) are crucial for understanding the
majority of cellular processes. PPIs play important role in gene transcription
regulation, cellular signaling, molecular basis of immune response and more.
Moreover, a disruption of hese mechanisms is frequently postulated as a
possible cause of diseases such as Alzheimer's or cancer. For many of
biologically relevant cases the structure of protein-protein complexes remain
unknown. Therefore computational techniques, including molecular docking, have
become a valuable part of drug discovery pipelines. Unfortunately, none of the
widely used protein-protein docking tools is free from serious limitations.
Typically, in docking simulations the protein flexibility is either completely
neglected or very limited. Additionally, some knowledge of the approximate
location and/or the shape of the active site is also required. Such limitations
arise mostly from the enormous number of degrees of freedom of protein-protein
systems. In this paper, an efficient computational method for protein-protein
docking is proposed and initially tested on a single docking case. The proposed
method is based on a two-step procedure. In the first step, CABS-dock web
server for protein-peptide docking is used to dock a peptide, which is the
appropriate protein fragment responsible for the protein-protein interaction,
to the other protein partner. During peptide docking, no knowledge about the
binding site, nor the peptide structure, is used and the peptide is allowed to
be fully flexible. In the second step, the docked peptide is used in the
structural adjustment of protein complex partners. The proposed method allowed
us to obtain a high accuracy model, therefore it provides a promising framework
for further advances.
