Advances in Computational Structure-Based Drug Design and Application in Drug Discovery

Compared with the increasing and widespread bacterial resistance to clinical medicines and the urgent need for cures of intractable diseases, there is a dramatic decline in the numbers of drugs reaching the market or clinical trials. Accordingly, it has become imperative to discover more rational and efficient strategies to design and develop novel drugs. Structure-based drug design/discovery (SBDD) is one of the computer-aided methods, by which novel drugs are designed or discovered based on the knowledge of 3D structures of the relevant specific targets. During the past few decades, the great potentials and success of SBDD have been seen in the field of drug discovery. In this review, we present an overview of the key mechanisms of SBDD, the frequently used computer programs in SBDD and the reported successful cases. Finally, several typical design processes of lead components from SBDD are also highlighted in detail, such as the discovery of inhibitors of G protein-coupled receptors (GPCRs), antibacterial drugs, and anti-cancer drugs.