English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

We study two designed and one natural zinc-finger peptide each with theCys2His2 (CCHH) type of metal binding motif. In the approach we have developed,we describe the role of the protein and solvent outside the Zn(II)-CCHHmetal-residue cluster by a molecular field represented by generalized harmonicrestraints. The strength of the field is adjusted to reproduce the bindingenergy distribution of the metal with the cluster obtained in a referenceall-atom simulation with empirical potentials. The quadratic field allows us toinvestigate analytically the protein restraints on the binding site in terms ofits eigenmodes. Examining these eigenmodes suggests, consistent withexperimental observations, the importance of the first histidine (H) in theCCHH cluster in metal binding. Further, the eigenvalues corresponding to thesemodes also indicate that the designed proteins form a tighter complex with themetal. We find that the bulk protein and solvent response tends to destabilizemetal-binding, emphasizing that the favorable energetics of metal-residueinteraction is necessary to drive folding in this system. The representation ofthe bulk protein and solvent response by a local field allows us to performMonte Carlo simulations of the metal-residue cluster using quantum-chemicalapproaches, here using a semi-empirical Hamiltonian. For configurations sampledfrom this simulation, we study the free energy of replacing Zn(II) with Fe(II),Co(II), and Ni(II) using density functional theory. The calculatedselectivities are in fair agreement with experimental results.

An elastic-network based local molecular field analysis of zinc-finger proteins