Journal of Enzyme Inhibition and Medicinal Chemistry

Mass Spectrometry in Medicinal Chemistry and Molecular Discovery

Mass spectrometry has become a central analytical platform in medicinal chemistry, informing research that spans small molecule discovery, peptide and protein therapeutics, biomolecular mechanism, and translational studies. The ability to measure molecular structures, define interactions, assess chemical stability, and characterise biological mixtures directly has made mass spectrometry a valued tool across early discovery through to optimisation and mechanistic interpretation. Increasing instrumental performance, improved ionisation strategies, high-resolution analysis and complementary data processing approaches now enable researchers to extract more detailed and biologically relevant information from complex systems. These developments have broadened access to mass spectrometry beyond the traditional analytical chemistry domain, with contributions from chemical biology, biophysics, metabolomics, proteomics, pharmaceutical sciences and clinical research. The versatility and impact of mass spectrometry continue to grow, creating opportunities for methodological innovation as well as for improved mechanistic insight that supports medicinal chemistry and molecular discovery.

Mass spectrometry provides information that is central to medicinal chemistry but often cannot be accessed by other analytical tools. It enables direct measurements of molecular structures, fragmentation patterns, binding interactions, post-translational regulation, and biological pathways, supporting confident interpretation of chemical and biological outcomes. This improves decision-making in early discovery, facilitates rational design of compounds, and helps define mechanisms relevant to therapeutic action and selectivity. In addition, the versatility of mass spectrometry allows researchers to analyse molecules under a range of solution conditions and biological contexts, linking chemical properties to pharmacologically meaningful behaviour. As new ionisation approaches, structural workflows, top-down and omics methods, automation strategies and data analytics continue to advance, there is a growing need to highlight how these capabilities can be applied effectively in medicinal chemistry. Bringing together examples that demonstrate practical value and mechanistic insight will support wider adoption, encourage innovation and guide researchers working across chemical and biological interfaces.

Mass spectrometry spans many subdisciplines relevant to medicinal chemistry, and this Collection aims to capture that breadth. Submissions may address native, denaturing or structural approaches; top-down or bottom-up workflows; ion mobility; affinity mass spectrometry; proteomics, metabolomics or lipidomics analyses; or translational studies that link molecular measurements to biological relevance. Methodological developments, instrumentation advances, sample-handling strategies, miniaturisation, high-throughput or automated formats, and data interpretation and modelling approaches are welcome. Applications involving ligand binding, molecular recognition, protein stability, selectivity and structure–activity assessment fit comfortably within scope, as do studies exploring mechanistic enzymology, chemical biology and pathway-level interrogation. We encourage both fundamental investigations and work with practical implications for drug discovery, pharmacology and diagnostics. The Collection will accept research articles, short communications, methodological papers, reviews and perspectives, consistent with the journal’s accepted article types. Our objective is to assemble a balanced set of contributions that reflect current capabilities and highlight emerging directions in this area.

Please submit your manuscript on our website, using the promo code IENZ-2026-C44701 for 10% off the advertised article processing charge and selecting the corresponding Article Collection title in the drop-down menu through the submission process to indicate that your manuscript will be considered for the “Mass Spectrometry in Medicinal Chemistry and Molecular Discovery” Collection.

Please contact Haoyang Yi (Commissioning Editor) at [email protected] with any queries regarding this Article Collection.

Guest Advisor

Prof. William Donald

William Alexander Donald is a Professor of Chemistry at UNSW Sydney, where his research focuses on the development and application of advanced mass spectrometry methods to study biomolecular systems. His work spans native mass spectrometry, proteomics, metabolomics and mechanistic studies relevant to medicinal chemistry. He has contributed to analytical methodology as well as applications in molecular recognition, structural characterisation and translational research. He has received national and international recognition for his research and collaborates widely across academia, industry and clinical partners.

Conflicts of Interest: Prof. William Donald holds equity and advisory roles with Preview Health and MassAffinity. His research has received support from Triana Biomedicines, Syntara, and All G Foods, and he collaborates with NSW Health Pathology. None of these relationships influence editorial decisions for this Article Collection.