Volume 5 Supplement 1
Targeting protein dynamics in drug design
© Wade; licensee BioMed Central Ltd. 2013
Published: 22 March 2013
The dynamic nature of protein structures provides challenges and opportunities for ligand design. I will first discuss some of the different ways in which protein dynamics can be targeted, giving examples from our experience in the design of inhibitors of thymidylate synthase [1–3]. I will then describe the development of a computational toolbox (TRAPP: TRAnsient Pockets in Proteins) to identify and visualize transient pockets in proteins that may be exploited in ligand design.
- Ferrari S, Costi MP, Wade RC: Inhibitor specificity via protein dynamics: Insights from design of antibacterial agents targeted against thymidylate synthase. Chem & Biol. 2003, 10: 1183-1193. 10.1016/j.chembiol.2003.11.012.View ArticleGoogle Scholar
- Salo-Ahen OMH, Wade RC: The Active-Inactive Transition of Human Thymidylate Synthase: Targeted Molecular Dynamics Simulations. Proteins: Struct, Funct, Bioinf. 2011, 79: 2886-2899. 10.1002/prot.23123.View ArticleGoogle Scholar
- Cardinale D, Guaitolia G, Tondi D, Luciani R, Henrich S, Salo-Ahen OMH, Ferrari S, Marverti G, Guerrieri D, Ligabue A, Frassineti C, Pozzi C, Mangani S, Fessas D, Guerrini R, Ponterini G, Wade R, Costi MP: Protein-protein interface-binding peptides inhibit the cancer therapy target human thymidylate synthase. Proc Natl Acad Sci USA. 2011, 108: 13889-13890. E542-E549View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.