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Journal Article

Binding affinities controlled by shifting conformational equilibria: Opportunities and limitations.

MPS-Authors
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Michielssens,  S.
Research Group of Computational Biomolecular Dynamics, MPI for Biophysical Chemistry, Max Planck Society;

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de Groot,  B. L.
Research Group of Computational Biomolecular Dynamics, MPI for Biophysical Chemistry, Max Planck Society;

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Grubmüller,  H.
Department of Theoretical and Computational Biophysics, MPI for biophysical chemistry, Max Planck Society;

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(Publisher version), 979KB

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Citation

Michielssens, S., de Groot, B. L., & Grubmüller, H. (2015). Binding affinities controlled by shifting conformational equilibria: Opportunities and limitations. Biophysical Journal, 108(10), 2585-2590. doi:10.1016/j.bpj.2015.04.012.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0027-7959-E
Abstract
Conformational selection is an established mechanism in molecular recognition. Despite its power to explain binding events, it is hardly used in protein/ligand design to modulate molecular recognition. Here, we explore the opportunities and limitations of design by conformational selection. Using appropriate thermodynamic cycles, our approach predicts the effects of a conformational shift on binding affinity and also allows one to disentangle the effects induced by a conformational shift from other effects influencing the binding affinity. The method is assessed and applied to explain the contribution of a conformational shift on the binding affinity of six ubiquitin mutants showing different conformational shifts in six different complexes.