On the calculation of absolute macromolecular binding free energies
AUTOR(ES)
Luo, Hengbin
FONTE
National Academy of Sciences
RESUMO
The standard framework for calculating the absolute binding free energy of a macromolecular association reaction A + B → AB with an association constant KAB is to equate chemical potentials of the species on the left- and right-hand sides of this reaction and evaluate the chemical potentials from theory. This theory involves (usually hidden) assumptions about what constitutes the bound species, AB, and where the contribution of the solvent appears. We present here an alternative derivation that can be traced back to Bjerrum, in which the expectation value of KAB is obtained directly through the statistical mechanical method of evaluating its ensemble (Boltzmann-weighted) average. The generalized Bjerrum approach more clearly delineates: (i) the different contributions to binding; (ii) the origin of the much-discussed and somewhat controversial association entropy term; and (iii) where the solvent contribution appears. This approach also allows approximations required for practical evaluation of the binding constant in complex macromolecular systems, to be introduced in a well defined way. We provide an example, with application to test cases that illustrate a range of binding behavior.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=124926Documentos Relacionados
- On the attribution and additivity of binding energies
- On the Theory of Ion Transport Across the Nerve Membrane, VI. Free Energy and Activation Free Energies of Conformational Change*
- Adhesion and motility of gliding bacteria on substrata with different surface free energies.
- Relative differences in the binding free energies of human immunodeficiency virus 1 protease inhibitors: a thermodynamic cycle-perturbation approach.
- Antibacterial Nitroacridine, Nitroakridin 3582: Binding to Nucleic Acids In Vitro and Effects on Selected Cell-Free Model Systems of Macromolecular Biosynthesis