title: Molecular dynamics study of enhanced Man5B enzymatic activity.
abstract: BACKGROUND
  Biofuels are a well-known alternative to the largely used fossil-derived fuels, however the competition with food production is an ethical dilemma. Fortunately a solution is offered by second-generation biofuels which can be produced from agricultural waste or, more specifically, from plant cell wall polysaccharides. The conversion process involves typically enzymatic hydrolysis of lignocellulosic biomass and then separation of its constituent sugars that are further fermented to produce ethanol. Over the years several technologies have been developed that allow this conversion process to occur and the objective is now to make this process cost-competitive in today's markets.
  
  
  RESULTS
  We observe that reduction of enzymatic efficiency in the presence of gluco-oligosaccharides is associated with a loss of the enzyme's flexibility, the latter being required to bind new substrate, while the presence of manno-oligosaccharides does not pose this problem. Molecular dynamics simulations identify key contacts between substrates and the enzyme catalytic pocket that might be modified through site-directed mutagenesis to prevent loss of enzymatic efficiency.
  
  
  CONCLUSIONS
  Based on previous experimental studies and the new molecular dynamics data, we suggest that cellohexaose in the active site pocket slows down or even inhibits Man5B enzymatic activity. The assumption of such a mechanism is reasonable since when the gluco-oligosaccharide substrate is attached to the catalytic pocket it takes much longer to leave the pocket and thus prevents other substrates from reaching the active site. The insight is of crucial importance since the inhibition of enzymes by the enzymatic product or by an unsuitable substrate is a major technological problem in reducing the competitiveness of second-generation biofuel production.
authors: Beckman Institute, University of Illinois, 405 N. Mathews Ave, Urbana, IL 61801, USA.
authors: Rafael C
authors: RC
authors: Bernardi
authors: Energy Biosciences Institute, University of Illinois, 1206 W. Gregory Dr, Urbana, IL 61801, USA ; Department of Microbiology, University of Illinois, 601 S. Goodwin Ave, Urbana, IL 61801, USA ; Department of Animal Science, University of Illinois, 1207 W. Gregory Dr, Urbana, IL 61801, USA ; Institute for Genomic Biology, University of Illinois, 1206 W. Gregory Dr, Urbana, IL 61801, USA.
authors: Isaac
authors: I
authors: Cann
authors: Beckman Institute, University of Illinois, 405 N. Mathews Ave, Urbana, IL 61801, USA ; Department of Physics, University of Illinois, 1110 W. Green St, Urbana, IL 61801, USA.
authors: Klaus
authors: K
authors: Schulten
keywords: Biofuel; Cellulase; Man5B; Mannanase; Molecular dynamics; Product inhibition