Methods for the design of molecular scaffolds and ligands

A method of designing a ligand that binds to at least one target molecule that is a member of a molecular family, comprising, identifying as molecular scaffolds one or more compounds that bind to binding sites of a plurality of members of a molecular family;

• determining the orientation of the one or more molecular scaffolds at the binding site of the target molecule to identify chemically tractable structures of the scaffolds that, when modified, alter the binding affinity or binding specificity between the scaffold and the target molecule;
• synthesizing a ligand wherein one or more of the chemically tractable structures of the molecular scaffold is modified to provide a ligand that binds to the target molecule with altered binding affinity or binding specificity.

A method for identifying binding characteristics of a ligand of a target protein, comprising

• identifying at least one conserved interacting residue in said target protein that interacts with at least two binding molecules;
• and
• identifying at least one common interaction property of said at least two binding molecules with said conserved residue, thereby identifying at least one said characteristic.

A method for identifying energetically allowed sites on a binding compound for attachment of an additional component, comprising analyzing the orientation of said binding compound in a target binding site, thereby identifying accessible sites on said compound of said separate component.

A method for attaching a binding compound to an attachment component, comprising

• identifying energetically allowed sites for attachment of a said attachment component on a binding compound;
• and
• attaching said compound or derivative thereof to said attachment component at said energetically allowed site.

A method for making an affinity matrix, comprising

• identifying energetically allowed sites on a target binding compound for attachment to a solid phase matrix;
• and
• attaching said target binding compound to said solid phase matrix through a said energetically allowed site.