engleski

Comparative binding energy (combine) analysis of barnase-barstar inter facial mutants

The extracellular ribonuclease barnase and its intracellular inhibitor barstar bind with high affinity. Even though the effects of mutations on binding have been extensively studied experimentally and theoretically, the relative importance of different contributions such as electrostatic interactions and interfacial water molecules to the binding affinity is still a topic of discussion. To address this problem, we have applied Poisson-Boltzmann electrostatic calculations and COMparative BINding Energy (COMBINE) analysis to derive quantitative structure-activity relationships (QSARs) for 65 barnase-barstar complexes with different interfacial mutations. The predictive QSAR models highlighted over 20 interfacial residue pairs as responsible for most of the differences in binding thermodynamics between the mutant complexes, mainly by their electrostatic interactions. The electrostatic desolvation energies of barnase and barstar also significantly contributed to the models.

Binding; Proteins; QSAR

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