Crystalline structure of human MAPKAP kinase-2

A method of growing crystals comprising:

• (a) providing a solution of MK-2 polypeptide molecules;
• (b) providing a precipitant solution comprising about 1.6 to about 2.6M ammonium sulfate, about 80-120 mM sodium acetate and about 2-50 mM of a crystallization additive;
• and
• (c) combining the solution of MK-2 polypeptide molecules with the precipitant solution and allowing crystals of protein MK-2 to form.

A computer-assisted method for identifying an inhibitor of MK-2 activity comprising:

• (a) supplying a computer modeling application with a set of structure coordinates of a molecule or molecular complex comprising at least a portion of an MK-2 or MK-2-like ATP binding site, the ATP binding site comprising amino acids 69-80, 90-95, 104, 108, 118-119, 136-147, 184-195,204-210,and224-226;
• (b) supplying the computer modeling application with a set of structure coordinates of a chemical entity;
• and
• (c) determining whether the chemical entity is an inhibitor expected to bind to or interfere with the molecule or molecular complex.

A computer-assisted method for designing an inhibitor of MK-2 activity comprising:

• (a) supplying a computer modeling application with a set of structure coordinates of a molecule or molecular complex comprising at least a portion of an MK-2 or MK-2-like ATP binding site, the ATP binding site comprising amino acids 69-80, 90-95, 104, 108, 118-119, 136-147, 184-195,204-210,and 224-226;
• (b) supplying the computer modeling application with a set of structure coordinates of a chemical entity;
• and
• (c) evaluating the potential binding interactions between the chemical entity and ATP binding site of the molecule or molecular complex;
• (d) structurally modifying the chemical entity to yield a set of structure coordinates for a modified chemical entity;
• and
• (e) determining whether the modified chemical entity is an inhibitor.

A computer-assisted method for designing an inhibitor of MK-2 activity de novo comprising:

• (a) supplying a computer modeling application with a set of structure coordinates of a molecule or molecular complex comprising at least a portion of an MK-2 or MK-2-like ATP binding site, the ATP binding site comprising amino acids 69-80, 90-95, 104, 108, 118-119, 136-147, 184-195,204-210, and 224-226;
• (b) computationally building a chemical entity represented by a set of structure coordinates;
• and
• (c) determining whether the chemical entity is an inhibitor expected to bind to or interfere with the molecule or molecular complex, wherein binding to or interfering with the molecule or molecular complex is indicative of potential inhibition of MK-2 activity.