(111b) Design and Computational Analysis of Protein Based Nanoscale Biomimetic Actuators

A nanoscale biomolecular linear actuator taken from a virus is described and methods to characterize and quantify its performance are discussed and applied. The HA2 domain of Influenza viral peptide in known to undergo a large conformational change in the cellular endosome upon a drop in pH. The peptide exists as a trimer with each monomer in the shape of an inverted hairpin. Upon pH drop or temperature increase, the outer arms of the monomers straighten, creating a linear motion, while the inner arms are stable coiled-coil structures due to hydrophobicity. The outer arms straighten to form extended coiled-coils and create a linear motion of ~10nm. It is proposed that this peptide, when isolated from the virus can be used in a variety of ways to create a nanoactuator for robotic devices performing controlled energy conversion. The main challenge in the design and performance analysis of nanodevices such as this, which are based on large conformational changes, is the limitation on computational time. A modified molecular dynamic approach known as Targeted Molecular Dynamics (TMD) is adopted to capture conformational changes within a smaller time frame (of the order of picoseconds). TMD technique is employed to study the opening/closing behavior of a hinge region that plays a critical role in the conformational change. Four different models of the peptide are subjected to TMD to trace a trajectory from closed (initial) to open (final) state and the differences between them are quantified using conformational energy and open state contacts to show the role of low pH as well as peptide mutations in order for such systems to act as nanoactuators. The results obtained are found to be in agreement with experimental findings that show that the protonated and mutated peptides are more likely to attain a stable open state in contrast to the wild type that does not display the same features.