Design of Alanine-Rich Short Peptides as a Green Alternative of Gas Hydrate Inhibitors: Dual Methyl Group Docking for Efficient Adsorption on the Surface of Gas Hydrates

As the source of fossil fuels moves toward gas, pipeline flow assurance has attracted considerable efforts in developing gas hydrate inhibitors, especially kinetic inhibitors (KIs), for prevention of gas hydrate formation inside pipelines. Traditional KIs are effective but show poor biodegradability that hinders practical use in specific regions, thus prompting search for new environmentally friendly KIs. Antifreeze proteins (AFPs) that evolved by nature to prevent ice growth are such candidates. However, the distinct differences in the crystal structures of hydrate and ice restrain the capability of AFPs in gas hydrate inhibition. We get inspiration from the type I AFP to design alanine-rich short peptides as a green alternative of KIs. Molecular dynamics simulations reveal the design principle, following which at least two methyl groups with coordinated spatial arrangement dock into neighboring cavities for achieving stable hydrate adsorption, which is key for the hydrate mitigation according to the adsorption-inhibition hypothesis. The mechanism of dual methyl group docking is evidenced by mutation and calculation of work profiles transferring peptides from the hydrate surface to the aqueous solution. By properly introducing lysine into the peptide, interestingly, the hydrate binding and inhibition can be enhanced as the bulky side chain in lysine eases peptide bending that enables more methyl groups docking into hydrate cages. These results can provide useful guidelines for the rational design of green effective hydrate inhibitors.