DynaFace: Discrimination between Obligatory and Non-obligatory Protein-Protein Interactions Based on the Complex's Dynamics.
Protein-protein interfaces have been evolutionarily-designed to enable transduction between the interacting proteins. Thus, we hypothesize that analysis of the dynamics of the complex can reveal details about the nature of the interaction, and in particular whether it is obligatory, i.e., persists throughout the entire lifetime of the proteins, or not. Indeed, normal mode analysis, using the Gaussian network model, shows that for the most part obligatory and non-obligatory complexes differ in their decomposition into dynamic domains, i.e., the mobile elements of the protein complex. The dynamic domains of obligatory complexes often mix segments from the interacting chains, and the hinges between them do not overlap with the interface between the chains. In contrast, in non-obligatory complexes the interface often hinges between dynamic domains, held together through few anchor residues on one side of the interface that interact with their counterpart grooves in the other end. In automatic analysis, 117 of 139 obligatory (84.2%) and 203 of 246 non-obligatory (82.5%) complexes are correctly classified by our method: DynaFace. We further use DynaFace to predict obligatory and non-obligatory interactions among a set of 300 putative protein complexes. DynaFace is available at: http://safir.prc.boun.edu.tr/dynaface.
Department of Computer Engineering and Polymer Research Center, Bogazici University, Istanbul, Turkey.
Seren
S
Soner
Department of Bioengineering, Marmara University, Istanbul, Turkey.
Pemra
P
Ozbek
Departments of Biochemistry and Molecular Biophysics and Systems Biology and Howard Hughes Medical Institute, Columbia University, New York, New York, United States of America.
Jose Ignacio
JI
Garzon
Department of Biochemistry and Molecular Biology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Nir
N
Ben-Tal
Department of Chemical Engineering and Polymer Research Center, Bogazici University, Istanbul, Turkey.
Turkan
T
Haliloglu
D000465:Algorithms; D001665:Binding Sites; D007700:Kinetics; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D046912:Multiprotein Complexes / Q000737:chemistry / Q000648:ultrastructure; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D012984:Software
D046912:Multiprotein Complexes; D011506:Proteins