Peptidomimetic compounds and related methods

A method for identifying a peptidomimetic compound that will perturb an interface region of a structurally characterized protein-protein interaction,

• wherein the interface region comprises a sequence of amino acids;
• and
• wherein the peptidomimetic compound comprises an organic scaffold bearing two or more amino acid side chains;
• the method comprising the steps of:
• (i) identifying one or more thermodynamically-preferred conformations of a template molecule, wherein the template molecule comprises the organic scaffold bearing two or more amino acid side-chains, wherein each amino acid side chain is methyl, and wherein the thermodynamically-preferred conformations have energies within 3 kcal/mol of the lowest energy conformation of the template molecule identified via molecular simulations;
• (ii) assigning three-dimensional coordinates to the Cα and Cβ atoms of the amino acid side chains in each conformation of the template molecule;
• (iii) assigning three-dimensional coordinates to the Cα and Cβ atoms of the amino acid side chains of the interface region;
• (iv) overlaying the coordinates from (ii) onto the coordinates of any two or more amino acid side chains from (iii) and selecting an overlay having a goodness-of-fit within a predetermined tolerance;
• and
• (v) identifying the peptidomimetic compound, wherein the amino acid side chains of the compound correspond to the amino acid side chains of the interface region of the overlay selected in step (iv).