# Sextant: A New Tool for Designing Custom Molecular Templates for Protein-Protein Interaction Inhibitor Drug Design

### Introduction

- Inhibiting Protein-Protein Interactions (PPIs) with small molecules is considered by many to be the most difficult area of drug discovery.
- Here we developed a method for designing custom templates into empty binding pockets and designed a library of small molecules to inhibit interaction human NPC1 and Zaire Ebolavirus (EBOV) GP1 protein.

(Panel A)

### Method

- The NPC1 pocket of interest without template molecule (Panel B) is the input for the Sextant process for building small molecule templates. (Panel C)
- QuADD returned a library of candidates, including 470 with dGs more favorable than the Sextant template. (Panel D)

### Conclusions

- The Sextant method designs templates into binding pockets.
- QuADD returns a strong candidate library (Panel E)
- This method can be applied to other protein pockets.
- This work is a part of a [DARPA IMPAQT contract. More details here.](https://polarisqb.com/polaris-news/polarisqb-receives-darpa-impaqt-funding-to-advance-quantum-computing-for-drug-design/)

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Authors: Byler, Kendall; Benson, Maurice; Petroff, Anna B.; Ingman, Victoria; Villar, Santiago; Hendrix, Paul; Simpson, William C.; Goldhagen, Guy; Shipman, William J.; Keinan, Shahar

Published On: November 10th, 2024