ABSTRACT

With recent advances in computer hardware and computational

methods, molecular modeling has been increasingly employed

to simulate biomolecules and materials, and demonstrated to

be powerful in elucidating new insights into structure-dynamics-

function relationships [1], as well as facilitating the design of new

drugs [2], catalysts and materials [3]. The foundation of molecular

modeling is ab initio quantum mechanics, which in principle would

provide the most rigorous potential energy surface to describe

a molecular system; however, its applicability to large systems

will be much limited for the foreseeable future due to its high

computational cost. Currently, to model most molecular processes

that do not involve chemical reactions, such as protein folding,

biomolecular recognition, and macromolecular assembly, a widely

applied method is the molecular mechanical force field. Meanwhile,

it has long been recognized that due to limitations in currently

available force fields, the power of molecular modeling has been

hampered.