Michael F. Crowley and Ross C. Walker

8.1 Introduction

Molecular modeling is a process employing a powerful set of tools for probing the atomistic mechanisms of cellulose hydrolysis, and will feature prominently in efforts to harness cel­lulose as a biomass energy resource. It provides a bridge between theoretical concepts and proposed mechanisms and the experimental data. Molecular modeling is most powerful when used in a synergistic fashion with experimentation where hypothesis-driven compu­tational research is used to help explain theoretical observations and to drive the design of future experiments. Molecular modeling encompasses the entire range of computational approaches available to the molecular biologist and it is beyond the scope of this book to give a comprehensive overview of all the computational models that exist. Instead we will concentrate on the subset of molecular modeling termed molecular dynamics, which will prove crucial in advancing our understanding of the behavior of celluloses and cellulases on the atomistic scale.

Molecular dynamics (MD) is generally used as a virtual experimental tool to probe the structure, function, kinetic, and thermodynamic properties of substances. In the biomolec­ular field, it has been invaluable in validating structures and elucidating mechanisms of structural stability and conformational change and for understanding interactions between molecules, their ligands, and their constituent parts. Most of MD is based on classical molec­ular mechanics (MM) with a smaller amount of work on using quantum mechanics (QM) with molecular mechanics to produce hybrid, QM/MM, dynamics methods. Although many of the computational methods used in molecular dynamics studies of biomolecular systems are mature, having been extensively applied to proteins, small molecules, and to nucleic acids, there has been, until recently comparatively little interest in the use of MD methods for carbohydrates and even less so for cellulose. The thrust of this chapter will be to doc­ument the current state of MD methods and MM force fields with the intent of inspiring greater use of the tools for the study of cellulosic recalcitrance to complement experimental studies, to answer questions that are unapproachable by current experimental technology, and to provide to experimentalists a wish list of new experimental targets, mutations, and structural information. We will include the work already accomplished, and outline the currently available methods and the kinds of questions they can answer for systems of the

Biomass Recalcitrance: Deconstructing the Plant Cell Wall for Bioenergy. Edited by Michael. E. Himmel © 2008 Blackwell Publishing Ltd. ISBN: 978-1-405-16360-6

size, complexity, and chemical nature of cellulose and the enzymes and other biomolecules that interact with it.