Rational design of bifunctional small molecules for protein-protein interactions

Overview

This research focuses on a novel methodology for the rational design of bifunctional small molecules to inhibit protein-protein interactions (PPIs), specifically targeting CD47-SIRP-alpha interactions. The approach leverages protein structural data to create molecules that bind to distinct sites on the proteins, thereby potentiating the inhibition of their interaction. This strategy has the potential to expand the realm of small molecule drug discovery beyond traditional enzyme-targeted approaches.

Technical specifications

Key Features:

• Utilizes computational methods such as protein-ligand docking, induced fit docking, and molecular dynamics to design bifunctional molecules.
• Focuses on two types of bifunctional molecules:
  • Type 1: Targets allosteric sites on CD47 and SIRP-alpha to weaken their interaction.
  • Type 2: Involves a shield protein (IsoQC) that modifies CD47, preventing interaction with SIRP-alpha.
• Aims to inhibit the CD47-SIRP-alpha interaction, potentially allowing immune cells to target tumor cells more effectively.

Technology readiness level

This research is at Technology Readiness Level 2, indicating that the technology is in the early stages of development with computational work currently underway. The project is focused on validating the binding affinity and structural conformational changes through these computational methods.