Stability of Tubular Structures Based on B-helical Proteins: Self-assembled Versus Polymerized Nanoconstructs and Wild-type Versus Mutated Sequences
In this work we used atomistic molecular dynamics simulations to examine different aspects of tubular nanostructures constructed using protein building blocks with a β-helical conformation. Initially, we considered two different natural protein building blocks, which were extracted from the protein data base, to compare the relative stabilities of the nanotubes obtained made of self-assembled and covalently linked repeats. Results show nanotubes constructed by linking building blocks through covalent bonds are very stable suggesting that the basic principles of polymer physics are valid when the repeating units are made of large fragments of proteins. In contrast, the stability of self-assembled nanostructures strongly depends on the attractive nonbonding interactions associated to building blocks aligned in a complementary manner. On the other hand, we investigated the ability of a conformationally constrained synthetic amino acid to enhance the stability of both self-assembled and polymerized nanotubes when it is used to substitute natural residues. Specifically, we considered 1-aminocyclopentane-1-caboxylic acid, which involves strong stereochemical constraints produced by the cyclopentane side chain. We found that the incorporation of this amino acid within the more flexible regions of the β-helical building blocks is an excellent strategy to enhance the stability of the nanotubes. Thus, when a single mutation is performed in the loop region of the β-helix, the bend architecture of the whole loop is stabilized since the conformational mobility is reduced not only at the mutated position but also at the adjacent positions.
Zheng, Jie, "Stability of Tubular Structures Based on B-helical Proteins: Self-assembled Versus Polymerized Nanoconstructs and Wild-type Versus Mutated Sequences" (2007). Chemical and Biomolecular Engineering Faculty Research. 278.