Enhancing computer-aided drug discovery through integration of quantum mechanics

The National Institute of General Medical Sciences awarded Middle Tennessee State University $125,700 on July 24, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to enhance computer-aided drug discovery through integration of quantum mechanics into structure-based drug design.

The project will revamp the computer-aided drug discovery (CADD) process by integrating quantum mechanical methods at critical computational steps, benchmark the performance of the quantum-enhanced CADD for computing ligand-protein complex structures and binding affinities, and design novel inhibitor molecules targeting the colchicine binding site of tubulin for cancer-related applications. The work addresses longstanding accuracy and chemical diversity limitations in empirical CADD models by applying highly efficient quantum methods developed by the principal investigator and co-investigator, reducing computational costs to enable practical quantum mechanical simulation of biological molecules in drug discovery workflows.

Performance of work occurs in Murfreesboro, Tennessee. The period of performance extends through May 31, 2030. Middle Tennessee State University is a state-controlled institution of higher learning operating primarily as a federal grant recipient across STEM research and education.

Abstract

This project aims to enhance drug design by integrating quantum mechanical methods into the structure-based computer-aided drug design (cadd) process and demonstrating the effectiveness of the quantum-enhanced cadd systematically and comprehensively. Furthermore, the new cadd will be applied to the design of novel inhibitors for tubulin, a protein related to many types of cancer. Cadd is an indispensable tool in drug discovery. However, despite its many successful applications, cadd has long suffered from the issue of low accuracy and limited chemical variety, mainly due to the empirical models employed. This leads to a high burden on the financial and labor costs of drug development. Applying the high- accuracy quantum mechanical methods have always been considered as the way to improve the accuracy of calculation, and subsequently the quality of cadd results. But the idea was never systematically realized in cadd due to the complexity and the high computational costs associated with QM methods. In the last two decades, the principal investigator and the CO-investigator have developed highly efficient quantum methods, making IT possible to simulate biological molecules hundreds of times faster when quantum mechanics is applied to the critical part of the simulation target. In this project, we plan to integrate those methods into the cadd process and demonstrate systematically how the quantum enhancement can improve drug discovery. The specific aims of this project are: (1) revamp the cadd process by integrating quantum mechanics at critical steps. (2) benchmark the performance of the new cadd for computing the structures and binding affinities of ligand-protein complexes. (3) design new potential HIT molecules with novel chemical structures to bind the colchicine binding site of tubulin. The success of this project will increase the trustworthiness of cadd and thus reduce the burden on experiments. IT will increase the overall efficiency of drug discovery and reduce its cost.