Dimeric interactions and complex formation using direct coevolutionary couplings

Autor(es)

dos Santos, Ricardo N. ^{[1, 2]} ; Morcos, Faruck ^[1] ; Jana, Biman ^[3] ; Andricopulo, Adriano D. ^[2] ; Onuchic, Jose N. ^[1]

Afiliação do(s) autor(es)

^[1] Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 - USA

^[2] Univ Sao Paulo, Inst Fis Sao Carlos, Lab Quim Med & Computac, BR-13563120 Sao Carlos, SP - Brazil

^[3] Indian Assoc Cultivat Sci, Dept Phys Chem, Kolkata 700032 - India

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 5, SEP 4 2015.
• Citações Web of Science: 29

Resumo

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 1.95 angstrom and 1.44 angstrom, 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. (AU)

• Processo FAPESP: 13/11950-0 - Estudos estruturais da polimerização de microtúbulos e sua modulação pela ação de fármacos anticâncer
• Beneficiário: Ricardo Nascimento dos Santos
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto