(575f) Computational Design of Novel Self-Assembling Peptide Biomaterials Based on an Amyloid Forming Motif from the Adenovirus Fiber Shaft
In the first part of the study, we used replica exchange MD simulations and free energy calculations, as in ref. (7,8) in CHARMM (9) to design a self-assembling amyloid peptide biomaterial with sequence RGDSGAITIGC (1). According to analysis of the simulations, the GAITIG motif is at the core of the fibril and is the motif leading to self-assembly (1,6,7,10), the cell-adhesive motif RGD at the N-terminal end is flexible and adequately solvent exposed to promote cell-adhesion, and the cysteine residue at the C-terminal domain is not part of the amyloid peptideâs amyloid zipper region, thus providing the biomaterial with metal binding properties. Experiments confirmed the bifunctional properties of the designed self-assembling amyloid peptide biomaterial which can be exploited for tissue engineering applications.
In the second part of the study, we introduced a novel in-house computational design protocol, which innovatively combines biophysical and optimization principles, and aimed at further stabilizing and potentially functionalizing the aforementioned self-assembling biomaterial by computationally and experimentally investigating additional mutations at the C-terminal end of the peptide. The mutations suggested by the computational protocol were investigated using replica exchange MD simulations and free energy calculations, and preliminary results from simulations and experiments confirm that the introduction of a specific amino acid substitution leads to a cell-adhesive self-assembling amyloid peptide biomaterial with promising advanced mechanical properties which can be further exploited in future tissue engineering applications.
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