Investigating the Role of the Cel7A Linker Peptide in Enzymatic Hydrolysis of Cellulose Chains: A Simulation Study

Free energy of the Cel7A linker peptide in water solution has been computed using molecular dynamics and umbrella sampling to investigate the possible role the linker plays in the hydrolysis of cellulose by Cel7A. Simulation results indicate that the free energy of the Cel7A linker depends critically on the existence of the cellulose substrate and the stretching/compression pathway adopted. In particular, a free linker shows distinct free energy profiles compared with that of the linker on cellulose surface. This implies that the interaction with the cellulose surface plays at least a partial role in determining the energy storage feature of the linker and thus is a significant factor in facilitating the functioning of the linker in the Cel7A enzyme. Secondly, folding of the linker along two different stretching/compression coordinates results in two completely different free energy profiles. In one pathway, a local energy minimum is observed which would allow the compressed linker to restore to its extended form. In the second pathway, a monotonic free energy profile was obtained if the minimum compressed length of the linker is greater than 15 A. Therefore, it is clear that in order for the linker to accumulate sufficient energy to switch between a compressed and extended state, it has to be compressed below a threshold length.