Dimeric interactions and complex formation using direct coevolutionary couplings.
We develop a procedure to characterize the association of protein structures into homodimers using coevolutionary couplings extracted from Direct Coupling Analysis (DCA) in combination with Structure Based Models (SBM). Identification of dimerization contacts using DCA is more challenging than intradomain contacts since direct couplings are mixed with monomeric contacts. Therefore a systematic way to extract dimerization signals has been elusive. We provide evidence that the prediction of homodimeric complexes is possible with high accuracy for all the cases we studied which have rich sequence information. For the most accurate conformations of the structurally diverse dimeric complexes studied the mean and interfacial RMSDs are 1.95Å and 1.44Å, respectively. This methodology is also able to identify distinct dimerization conformations as for the case of the family of response regulators, which dimerize upon activation. The identification of dimeric complexes can provide interesting molecular insights in the construction of large oligomeric complexes and be useful in the study of aggregation related diseases like Alzheimer's or Parkinson's.
Center for Theoretical Biological Physics, Rice University, Houston, TX 77005-1827.|Laboratório de Química Medicinal e Computacional, Instituto de Física de São Carlos, Universidade de São Paulo, São Paulo, São Carlos, 13563-120, Brazil.
Ricardo N
RN
dos Santos
Center for Theoretical Biological Physics, Rice University, Houston, TX 77005-1827.
Faruck
F
Morcos
Department of Physical Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata-700032, India.
Biman
B
Jana
Laboratório de Química Medicinal e Computacional, Instituto de Física de São Carlos, Universidade de São Paulo, São Paulo, São Carlos, 13563-120, Brazil.
Adriano D
AD
Andricopulo
Center for Theoretical Biological Physics, Rice University, Houston, TX 77005-1827.
José N
JN
Onuchic
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D003198:Computer Simulation; D019281:Dimerization; D019143:Evolution, Molecular; D008957:Models, Genetic; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D011485:Protein Binding / Q000235:genetics; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics* / Q000648:ultrastructure; D020539:Sequence Analysis, Protein / Q000379:methods
D046912:Multiprotein Complexes; D011506:Proteins