Multiscale Computer Simulation on Cellulase: Protein Allostery on Solid-Liquid Interface and Cellulose Deconstruction


Yuchun Lin, UC Berkeley


2012.03.06 21:00-22:00


601 Pao Yue-Kong Library


At phase boundaries, physical activities of enzymes such as substrate complexation play critical roles in driving biocatalysis. A prominent example is the cellulase cocktails secreted by fungi and bacteria for deconstructing crystalline cellulose in biomass into soluble sugars. At interfaces,molecular mechanisms of the physical steps in biocatalysis remain elusive due to the difficulties of characterizing protein action with high temporal and spatial resolution. In this talk, I will present our recent results which focuses on endoglucanase I (Cel7B) from the fungus Trichoderma reesei that hydrolyzes glycosidic bonds on cellulose randomly. We employ all-atom molecular dynamics (MD) simulations to elucidate the interactions of the catalytic domain (CD) of Cel7B with a cellulose microfibril before and after complexing a glucan chain in the binding cleft. The calculated mechanical coupling networks in Cel7B_glucan and Cel7B_microfibril complexes reveal a previously unresolved allosteric coupling at the solid_liquid interface: attachment of the Cel7B CD to the cellulose surface affects glucan chain clenching in the binding cleft. Alternative loop segments of the Cel7B CD were found to affix to intact or defective surface structures on the microfibril, depending on the complexation state. From a multiple sequence alignment, residues in surface-affixing segments show strong conservation, highlighting the functional importance of the physical activities that they facilitate. Surface-affixing residues also demonstrate significant sequence correlation with active-site residues, revealing the functional connection between complexation and hydrolysis. Free-energy profiles for this complexation process will be also presented and discussed.