Ahmed M Ali

Assiut University, Asyūţ, Muhafazat Asyut, Egypt

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Publications (2)6.95 Total impact

  • Ahmed M Ali, G Andrew Woolley
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    ABSTRACT: Photo-switchable α-helical peptides offer a valuable tool to probe protein-biomacromolecule interactions in a spatiotemporally controlled manner. We synthesized a series of 32 residue peptides (AA32 s) with the core structure Ac-W-(E1A2A3A4R5)6-Q-NH2 and introduced the azobenzene based cross-linker BSBCA via reaction with Cys residues spaced at i, i + 7 intervals in different positions along the helix. UV/Vis measurements show that the composition of the photostationary state as well as thermal relaxation rates do not change considerably with changes in cross-linker position. CD analysis shows that photo-control of helix folding/unfolding is most effective when the cross-linker is targeted to the middle of the peptide so long as this segment has a high intrinsic helical propensity. The largest degree of photo-controlled conformational change occurred when a cross-linked central region of high intrinsic helicity was followed on the C-terminal side by a region of lower intrinsic helicity. This indicates the BSBCA cross-linker can act as a nucleation site for N-to-C propagation of a helix. These data help to guide the choice of cross-linking site in larger peptides and proteins where photo-control of conformation is desired.
    Organic & Biomolecular Chemistry 07/2013; · 3.57 Impact Factor
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    ABSTRACT: Photoswitchable distance constraints in the form of photoisomerizable chemical cross-links offer a general approach to the design of reversibly photocontrolled proteins. To apply these effectively, however, one must have guidelines for the choice of cross-linker structure and cross-linker attachment sites. Here we investigate the effects of varying cross-linker structure on the photocontrol of folding of the Fyn SH3 domain, a well-studied model protein. We develop a theoretical framework based on an explicit-chain model of protein folding, modified to include detailed model linkers, that allows prediction of the effect of a given linker on the free energy of folding of a protein. Using this framework, we were able to quantitatively explain the experimental result that a longer, but somewhat flexible, cross-linker is less destabilizing to the folded state than a shorter more rigid cross-linker. The models also suggest how misfolded states may be generated by cross-linking, providing a rationale for altered dynamics seen in nuclear magnetic resonance analyses of these proteins. The theoretical framework is readily portable to any protein of known folded state structure and thus can be used to guide the design of photoswitchable proteins generally.
    Biochemistry 07/2012; 51(32):6421-31. · 3.38 Impact Factor