(557f) Cellulase Peripheral Loops Facilitate Complexation On Cellulose Via Whole-Path Stabilization

The structure-function relationships of complexation of cellodextrin chains from cellulose crystals into the active site of a glycoside hydrolase family 7 endoglucanase catalytic domain (Cel7B CD) are revealed via atomistic molecular dynamics simulations, reaction path optimization, and free-energy calculations. In addition, we characterized the evolving enzyme-microfibril interactions through the complexation process by analyzing the atomistic simulations with a coarse graining procedure. We found that the semi-open active site of Cel7B CD exhibits similar barriers and free energies of complexation over two distinct pathways, namely scooping of a chain into the active site cleft and threading from the chain end into the channel. Both the scooping and threading paths were observed to proceed with similar energetics in complexing glucan chains of different arrangements on the cellulose surface. An emergent principle is that Cel7B CD facilitates the cellulose processing via whole-path stabilization. The peripheral peptide segments outside the active site cleft are shown to couple to the evolving surface structures of cellulose over the simulated paths. The sequence patterns of this functionality were revealed via the approach of mapping atomistic fluctuations onto the parameters of a coarse-grain model. The adopted strategy of linking physics-based molecular interactions to protein sequence could also be employed to elucidate the principles of other protein machines in processing biopolymers.