Kang, C., Song, H., & Xu, W. (2025). Structural and Computational Biology: Compete or Complement? Journal of Medicinal Chemistry, 68(23), 24721–24723. https://doi.org/10.1021/acs.jmedchem.5c03284
Abstract:
Over the last century, structural biology has evolved with advances in X-ray crystallography, nuclear magnetic resonance (NMR) and cryo-electron microscopy (cryo-EM) to determine three-dimensional structures of macromolecules at an atomic resolution, consolidating a rational basis for drug discovery and design via structure-guided approaches. Owing to their inherent characteristics, these methods are often used for specific applications in biological and pharmaceutical research. Over the past few decades, X-ray crystallography has played a pivotal role in structure-based drug design (SBDD), leading to the successful development of several FDA-approved drugs including Tamiflu, a neuraminidase inhibitor to treat influenza; Darunavir, an HIV protease inhibitor; Imatinib (Gleevec), a type II tyrosine kinase (BCR-ABL) inhibitor for treating chronic myelogenous leukemia (CML); and Vemurafenib, a mutant BRAFV600E kinase inhibitor for the treatment of melanoma. NMR spectroscopy has been applied to determine structures of macromolecules such as highly dynamic molecules including RNAs ad intrinsically disordered proteins, transmembrane proteins, high-molecular weight complexes and different conformers. In recent years, cryo-electron microscopy (cryo-EM) has revolutionized structural biology by enabling direct visualization of biomolecules in diverse conformational states, thus revealing the dynamic “structural landscape” of proteins and RNAs rather than a single static snapshot. For proteins and large complexes, cryo-EM resolves distinct functional states, reaction intermediates, and conformational transitions through image sorting and 3D classification of single-particle data, allowing structural biologists to capture motions intrinsically tied to biological function. Combined with other techniques like mass spectrometry (MS) and small-angle X-ray scattering (SAXS), these experimental techniques play interchangeable role for aiding our understanding toward structural information of biological systems.
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Funding Info:
This research is supported by core funding from: Experimental Drug Development Centre (EDDC)
Grant Reference no. : Core
This research / project is supported by the A*STAR - PREPARE
Grant Reference no. : CS1-2025-016