results in new combined scoring function HPNet-combine. It was found that
HPNet-combine could improve the discrimination of the RosettaDock scoring
function.
The similar methodology based on the construction of a hydrophobic and hydrophilic RINs of protein–protein complexes was used for the development NPPD
scoring function [67]. Protein–protein docking, HoDock, and scoring function
HPNCscore (hydrophobic, and polar network combined scoring function) were
developed. It showed good results for several targets in Critical Assessment of
PRedicted Interactions (CAPRI) rounds [68].
The weighed RINs were used for the development of Sn scoring function [69].
Two weighted parameters (strength and weighted average nearest neighbors’
degree) were introduced to develop a scoring function. The testing of this scoring
function for 42 protein–protein complexes had shown a satisfied performance.
The scoring function based on the local network patterns, iScore, was proposed
[70]. It achieved 83.6% specificity with 82% sensitivity for training set of *1800
two domain proteins, homo- and heterodimers.
3.3 Allosteric Regulation
Allosteric regulation is a common mechanism to control the protein activities. The
perturbation at the allosteric site results in transmission of signal through the protein
structure to other sites leading to modification of catalytic activity, oligomerization,
etc. [71, 72].
Allosteric sites became attractive target for drug design at last decade. Allosteric
drugs have several potential benefits over orthosteric drugs. They may be more
specific due to less similarity of allosteric sites comparing to active site in
homologous proteins; they can increase or decrease the activity of enzymes and
receptors; partially inhibiting by allosteric drugs may cause less side effects [73,
72].
Using allosteric sites for drug design, it is required to predict allosteric sites,
residues involved in signal transduction pathways to the active sites. The search of
allosteric sites by RIN method is similar to the other sites described above.
Allosteric pathways show how the signal may be transmitted over a long distance from allosteric to active sites within the protein. RIN is accurate and not
time-consuming method for prediction such pathways.
Once the RIN constructed, several algorithms can be used to find allosteric
pathways within the RINs. The common method is to find the shortest paths
connecting the allosteric and active sites [34, 35, 74]. The shortest path may be
determined by Floyd–Warshall algorithm. It was shown that many proteins may be
considered as a set of modules (subgraphs with many interconnections and with few
connections to other subgraphs). The residues involved in the interaction of such
modules can participate in allosteric pathways [75]. It is proposed that such residues
are conservative that also may be used for their prediction [76–78]. Proteins can
Analysis of Protein Structures Using Residue Interaction …
61
HPNet-combine could improve the discrimination of the RosettaDock scoring
function.
The similar methodology based on the construction of a hydrophobic and hydrophilic RINs of protein–protein complexes was used for the development NPPD
scoring function [67]. Protein–protein docking, HoDock, and scoring function
HPNCscore (hydrophobic, and polar network combined scoring function) were
developed. It showed good results for several targets in Critical Assessment of
PRedicted Interactions (CAPRI) rounds [68].
The weighed RINs were used for the development of Sn scoring function [69].
Two weighted parameters (strength and weighted average nearest neighbors’
degree) were introduced to develop a scoring function. The testing of this scoring
function for 42 protein–protein complexes had shown a satisfied performance.
The scoring function based on the local network patterns, iScore, was proposed
[70]. It achieved 83.6% specificity with 82% sensitivity for training set of *1800
two domain proteins, homo- and heterodimers.
3.3 Allosteric Regulation
Allosteric regulation is a common mechanism to control the protein activities. The
perturbation at the allosteric site results in transmission of signal through the protein
structure to other sites leading to modification of catalytic activity, oligomerization,
etc. [71, 72].
Allosteric sites became attractive target for drug design at last decade. Allosteric
drugs have several potential benefits over orthosteric drugs. They may be more
specific due to less similarity of allosteric sites comparing to active site in
homologous proteins; they can increase or decrease the activity of enzymes and
receptors; partially inhibiting by allosteric drugs may cause less side effects [73,
72].
Using allosteric sites for drug design, it is required to predict allosteric sites,
residues involved in signal transduction pathways to the active sites. The search of
allosteric sites by RIN method is similar to the other sites described above.
Allosteric pathways show how the signal may be transmitted over a long distance from allosteric to active sites within the protein. RIN is accurate and not
time-consuming method for prediction such pathways.
Once the RIN constructed, several algorithms can be used to find allosteric
pathways within the RINs. The common method is to find the shortest paths
connecting the allosteric and active sites [34, 35, 74]. The shortest path may be
determined by Floyd–Warshall algorithm. It was shown that many proteins may be
considered as a set of modules (subgraphs with many interconnections and with few
connections to other subgraphs). The residues involved in the interaction of such
modules can participate in allosteric pathways [75]. It is proposed that such residues
are conservative that also may be used for their prediction [76–78]. Proteins can
Analysis of Protein Structures Using Residue Interaction …
61