p53 is a powerful anti-tumoral molecule frequently inactivated by mutations or deletions in cancer. However, half of all human tumors expresses wild-type p53, and its activation, by antagonizing its negative regulator Mdm2, might offer a new strategy for therapeutic protocol. In this work, we present a molecular dynamics study on Mdm2 structure bound to two different known inhibitors with the aim to investigate the structural transitions between apo-Mdm2 and Mdm2-inhibitor complexes. We tried to gain information about conformational changes binding a benzodiazepine derivative inhibitor with respect the known nutlin and the apo form. The conformational changes alter the size of the cleft and were mainly in the linker regions, suggesting that the overall dynamic nature of Mdm2 is related to dynamic movements in these regions.

ALMERICO, A.M., TUTONE, M., PANTANO L, LAURIA, A. (2012). Molecular Dynamics studies on Mdm2 complexes: an analysis of the inhibitor influence. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 424(424), 341-347 [http://dx.doi.org/10.1016/j.bbrc.2012.06.138].

Molecular Dynamics studies on Mdm2 complexes: an analysis of the inhibitor influence

ALMERICO, Anna Maria;TUTONE, Marco;PANTANO, Licia;LAURIA, Antonino
2012-01-01

Abstract

p53 is a powerful anti-tumoral molecule frequently inactivated by mutations or deletions in cancer. However, half of all human tumors expresses wild-type p53, and its activation, by antagonizing its negative regulator Mdm2, might offer a new strategy for therapeutic protocol. In this work, we present a molecular dynamics study on Mdm2 structure bound to two different known inhibitors with the aim to investigate the structural transitions between apo-Mdm2 and Mdm2-inhibitor complexes. We tried to gain information about conformational changes binding a benzodiazepine derivative inhibitor with respect the known nutlin and the apo form. The conformational changes alter the size of the cleft and were mainly in the linker regions, suggesting that the overall dynamic nature of Mdm2 is related to dynamic movements in these regions.
Settore CHIM/08 - Chimica Farmaceutica
ALMERICO, A.M., TUTONE, M., PANTANO L, LAURIA, A. (2012). Molecular Dynamics studies on Mdm2 complexes: an analysis of the inhibitor influence. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 424(424), 341-347 [http://dx.doi.org/10.1016/j.bbrc.2012.06.138].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/64272
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