Abstract: Methods of using monoclinic crystals of human beta-secretase (BACE) having unit cell dimensions of a, b, and c, wherein a is about 81±20 ? to about 101 ?, b is 103±20 ?, c is 100±20 ?, and ?=?=90°, and ? is 105°±10° for crystals of symmetry P21 and a=73.1, b=105.1, c=50.5 ? and ? is 94.8° for crystals of C2 symmetry in drug screening assays comprising selecting a potential modifier by adding the potential modifiers to an aqueous mixture of the crystal and detecting a measure of binding, such that the potential modifier that binds is selected as a potential drug.

Abstract: The x-ray crystal structure of human BACE or BACE-like proteins is useful for solving the structure of other molecules or molecular complexes, and identifying and/or designing potential modifiers of human BACE activity.

Abstract: The present invention provides a crystal of human beta-secretase (BACE) having monoclinic space group symmetry C2, in a representative example, comprising a unit cell having dimensions of a, b, and c, wherein a is about 53 ? to about 103 ?, b is about 85 ? to about 125 ?, c is about 40 ? to about 60 ?, and ?=?=90°, and ? is about 85° to about 105°, and in a preferred example, comprising unit cell dimensions as follows: a is 73.1 ?, b is 105.1 ?, c is 50.5 ?, and ?=?=90°, and ? is 94.8, wherein the Matthews coefficient of said crystal is 2.1 ?/Da with 42% solvent, and wherein said crystal diffracts to 1.7 ? resolution.