BSc(Hons) Chemistry, University College Dublin.
PhD Computational Chemistry, University of Dublin, Trinity College.
Research combines computational techniques such as docking, molecular mechanics and dynamics, quantum chemistry and hybrid quantum mechanics/molecular mechanics (QM/MM) methods to investigate biological processes. In structure based drug (inhibitor) design (SBDD), for example, modeling calculations can speed up the identification of good inhibitors and reduce the time spent on costly laboratory procedures.
In this respect, computation can be used to guide the choice of experiment.
Recent modeling work has focused on the control of glycogenolysis towards a new type II diabetes therapy. Two target enzymes are being studied: Glycogen Phosphorylase (GP) and Phosphorylase Kinase (PhK). Using a multidisciplinary approach involving close collaboration with synthetic chemists, crystallographers and molecular biologists, some of the most potent inhibitors of GP have been identified. Work on PhK (a heterotetramer (αβγδ)4) is at a much earlier stage, and given the difficulties associated with the crystallization of the kinase domain (γ subunit) with inhibitors, computation provides a valuable alternative research tool. Moreover, in collaboration with Prof. Martin Caffrey at Trinity College Dublin, GPR40 is now also being investigated as a target for type II diabetes treatment. Other recent modeling applications have studied the pharmacokinetic properties of Bovine Seminal RiboNuclease (BS-RNase) inhibitors (towards potential anti-cancer therapy); investigated the structure, function and mechanisms of the human Coilin Interacting Nuclear ATPase Protein (hCINAP); and analyzed the binding and action of antihypertensive drug Valsartan. Further research interests lie in the areas of chiral separation and the design of synthetic receptors for this purpose, and the determination of reaction mechanisms using QM and QM/MM techniques.
Selected Recent Publications:
Hayes JM*, Skamnaki VT, Archontis G, Lamprakis C, Sarrou J, Bischler N, Skaltsounis AL, Zographos SE, and Oikonomakos NG, "Kinetics, in silico docking, molecular dynamics and MM-GBSA binding studies on prototype indirubins, KT5720 and staurosporine as phosphorylase kinase ATP-binding site inhibitors: the role of water molecules examined", Proteins: Structure, Function & Bioinformatics (2011), 79, 703-719.
Hayes JM*, Leonidas DD, "Computation as a tool for glycogen phosphorylase inhibitor design", Mini Rev. Med. Chem. (2010), 10, 1156-1174.
Benltifa M, Hayes JM, Vidal S, Gueyrard D, Goekjian PG, Praly JP,* Kizilis G, Tiraidis C, Alexacou K-M, Chrysina ED*, Zographos SE, Leonidas DD, Archontis G, and Oikonomakos NG, "Glucose-based Spiro-isoxazolines: A New Family of Potent Glycogen Phosphorylase Inhibitors", Biorg. Med. Chem. (2009), 17, 7368-7380.