The Interacting Quantum Atoms energy partitioning in a fragment-based drug design setting: a set of case studies

Abstract

The Interacting Quantum Atoms energy partition technique (IQA) is an Energy Decomposition Analysis in the framework of Quantum Chemical Topology. IQA has had success in explaining different phenomena in physical chemistry. Because of the computational cost of the technique, it has been used in small chemical systems, up to dozens of atoms. This work seeks to push the practical boundaries of IQA calculations, using the technique in chemical system sizes that have not been explored in this framework. We do this by applying the IQA partition in Quantum Mechanical cluster models of proteins complexed with their inhibitors. The fragment-based drug design approach lends itself to a multiple stages comparison using IQA as the drug candidate is improved. The inhibitors are analysed at different stages of the design process and the IQA partition is obtained and compared. The work contained in this report consists in the largest systems in which the Interacting Quantum Atoms technique has ever been used. It also demonstrates IQA is robust and can have a lot to say in drug design scenarios.

Date of Award	5 Dec 2018
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Paul Popelier (Main Supervisor) & Neil Burton (Co Supervisor)