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Pregled bibliografske jedinice broj: 153143

How Optimal Are the Binding Energetics of Barnase and Barstar?

Wang, Ting; Tomić, Sanja; Gabdoulline, Razif; Wade, Rebecca
How Optimal Are the Binding Energetics of Barnase and Barstar? // Biophysical journal, 87 (2004), 1618-1630 (međunarodna recenzija, članak, znanstveni)

How Optimal Are the Binding Energetics of Barnase and Barstar?

Wang, Ting ; Tomić, Sanja ; Gabdoulline, Razif ; Wade, Rebecca

Biophysical journal (0006-3495) 87 (2004); 1618-1630

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Protein-protein interaction; molecular modeling; QSAR

The extracellular ribonuclease barnase and its intracellular inhibitor barstar bind fast and with high affinity. Although extensive experimental and theoretical studies have been carried out on this system, it is unclear what the relative importance of different contributions to the high affinity is and whether binding can be improved through point mutations. In this work, we first applied Poisson-Boltzmann electrostatic calculations to 65 barnase-barstar complexes with mutations in both barnase and barstar. The continuum electrostatic calculations with a van der Waals surface dielectric boundary definition result in the electrostatic interaction free energy providing the dominant contribution favoring barnase-barstar binding. The results show that the computed electrostatic binding free energy can be improved through mutations at W44/barstar and E73/barnase. Furthermore, the determinants of binding affinity were quantified by applying COMparative BINding Energy (COMBINE)analysis to derive quantitative structure-activity relationships (QSARs) for the 65 complexes. The COMBINE QSAR model highlights ~20 interfacial residue pairs as responsible for most of the differences in binding affinity between the mutant complexes, mainly due to electrostatic interactions. Based on the COMBINE model, together with Brownian dynamics simulations to compute diffusional association rate constants, several mutants were designed to have higher binding affinities than the wild-type proteins.

Izvorni jezik

Znanstvena područja


Projekt / tema

Institut "Ruđer Bošković", Zagreb

Autor s matičnim brojem:
Sanja Tomić, (113604)

Časopis indeksira:

  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus