IMR Press / FBL / Volume 16 / Issue 5 / DOI: 10.2741/3809

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Bridging quantum mechanics and structure-based drug design
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1 Department of Drug Discovery and Development, Italian Institute of Technology, via Morego 30, I-16163 Genova, Italy

Academic Editor: Andrea Cavalli

Front. Biosci. (Landmark Ed) 2011, 16(5), 1619–1633;
Published: 1 January 2011
(This article belongs to the Special Issue Computational medicinal chemistry and drug design)

The last decade has seen great advances in the use of quantum mechanics (QM) to solve biological problems of pharmaceutical relevance. For instance, enzymatic catalysis is often investigated by means of the so-called QM/MM approach, which uses QM and molecular mechanics (MM) methods to determine the (free) energy landscape of the enzymatic reaction mechanism. Here, I will discuss a few representative examples of QM and QM/MM studies of important metalloenzymes of pharmaceutical interest (i.e. metallophosphatases and metallo-beta-lactamases). This review article aims to show how QM-based methods can be used to elucidate ligand-receptor interactions. The challenge is then to exploit this knowledge for the structure-based design of new and potent inhibitors, such as transition state (TS) analogues that resemble the structure and physicochemical properties of the enzymatic TS. Given the results and potential expressed to date by QM-based methods in studying biological problems, the application of QM in structure-based drug design will likely increase, making of these once-prohibitive computations a routinely used tool for drug design.

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