IBM and NeSC workshop on Protein Science
National e-Science Centre, Edinburgh, March
15-16 2002
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Investigation of the binding mode of progesterone to its receptor by Molecular Dynamics simulations Tiziana Mordasini, Alessandro Curioni and Wanda Andreoni IBM Research, Zurich Research Laboratory, 8803 Rüschlikon, Switzerland Roberta Bursi Molecular Design & Informatics Department, N. V. Organon, 5340 BH Oss, The Netherlands Progesterone, a steroid hormone present in all vertebrates and acting as transcription regulator, is involved in a large number of biological activities. For many years the interaction of human progesterone and its receptor has been the target of study related to numerous pharmacological applications ranging from oral contraception, to cancer and hormone-replacement therapies. Some of the characteristics have been clarified by the refinement of the structure of the ligand-binding domain of the progesterone-receptor complex. However, contrary to the expectation that both keto-groups at the ends of the progesterone would be involved in the binding, these X-ray studies indicate that one of them plays no role, thus a series of questions and speculations. Using classical Molecular Dynamics simulations, we have investigated the ligand-protein binding. Partner residues are well identified and the role of water is elucidated. The results are also compared with the available experimental data. |
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