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Targeting protein dynamics in drug design

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 [13]. 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.


  1. 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.

    Article  CAS  Google Scholar 

  2. 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.

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  3. 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-E549

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Correspondence to Rebecca C Wade.

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Wade, R.C. Targeting protein dynamics in drug design. J Cheminform 5 (Suppl 1), O1 (2013).

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