SUPR
Predicting variant-induced drug resistance by combining artificial intelligence with deep mutational scanning and 3D protein-drug complex structures
Dnr:

NAISS 2024/22-752

Type:

NAISS Small Compute

Principal Investigator:

Yoomi Park

Affiliation:

Karolinska Institutet

Start Date:

2024-06-05

End Date:

2025-06-01

Primary Classification:

10201: Computer Sciences

Webpage:

Allocation

Abstract

Genetic variants can influence drug efficacy by altering the binding affinity of drugs to their protein targets. To understand how specific genetic variants disrupt protein-drug binding and impact drug efficacy, our project integrates artificial intelligence with deep mutational scanning and structural analysis of 3D protein-drug complexes. The project has four key objectives: (a) experimentally determining the functionality of all possible MDR1 transporter variants across multiple drugs, (b) calculating the impact of genetic variants on drug binding by linking 3D protein structures with genetic data, (c) developing AI models to predict drug efficacy changes due to genetic variants, including those not experimentally investigated, and (d) implementing a clinical decision support system for precision dosing and drug selection. This approach empowers physicians to formulate optimal management strategies, advancing personalized medicine and enhancing healthcare competitiveness.