Related Experiment Video
Updated: Aug 29, 2026

Bio-layer Interferometry for Measuring Kinetics of Protein-protein Interactions and Allosteric Ligand Effects
Published on: February 18, 2014
Inhibitor specificity via protein dynamics: insights from the design of antibacterial agents targeted against
Stefania Ferrari1, Paola M Costi, Rebecca C Wade
1Dipartimento di Scienze Farmaceutiche, Università di Modena e Reggio Emilia, Via Campi 183, 41100 Modena, Italy. ferrari.stefania@unimore.it
Abstract:
Structure-based drug design of species-specific inhibitors generally exploits structural differences in proteins from different organisms. Here, we demonstrate how achieving specificity can be aided by targeting differences in the dynamics of proteins. Thymidylate synthase (TS) is a good target for anticancer agents and a potential target for antibacterial agents. Most inhibitors are folate-analogs that bind at the folate binding site and are not species specific. In contrast, alpha156 is not a folate-analog and is specific for bacterial TS; it has been shown crystallographically to bind in a nonconserved binding site. Docking calculations and crystal structure-based estimation of the essential dynamics of TSs from five different species show that differences in the dynamics of TSs make the active site more accessible to alpha156 in the prokaryotic than in the eukaryotic TSs and thereby enhance the specificity of alpha156.
More Related Videos
10:01Structure-Guided Design and Development of Novel Cyclophilin A Inhibitors and Ganoderiol-F Derivatives: An In-Silico Approach
Published on: June 23, 2026
10:33Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
Published on: October 26, 2015
Related Concept Videos
Inhibitors of Bacterial Protein Synthesis
Inhibitors of Bacterial DNA Synthesis
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Enzymes
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
Enzyme Inhibition
Inhibitors of Gram-positive Cell Wall Synthesis