DUGi

Electronic structure investigation and parametrization of biologically relevant iron-sulfur clusters

http://dugi.udg.edu/item/http:@@@@hdl.handle.net@@10256@@11451

The application of classical molecular dynamics simulations to the study of metalloenzymes has been hampered by the lack of suitable molecular mechanics force field parameters to treat the metal centers within standard biomolecular simulation packages. These parameters cannot be generalized, nor be easily automated, and hence should be obtained for each system separately. Here we present density functional theory calculations on [Fe2S 2(SCH3)4]2+/+, [Fe3S 4(SCH3)3]+/0 and [Fe 4S4(SCH3)4]2+/+ and the derivation of parameters that are compatible with the AMBER force field. Molecular dynamics simulations performed using these parameters on respiratory Complex II of the electron transport chain showed that the reduced clusters are more stabilized by the protein environment, which leads to smaller changes in bond lengths and angles upon reduction. This effect is larger in the smaller iron-sulfur cluster, [Fe2S2(SCH3) 4]2+/+

The following organizations are thanked for financial support: The AGAUR for the fellowship 2010 BP_B00238, the Ministerio de Ciencia e Innovacion (MICINN, project number CTQ2011-25086/BQU) and the DIUE of the Generalitat de Catalunya (project number 2009SGR528, and Xarxa de Referencia en Quimica Teorica i Computacional). Financial support from MICINN (Ministry of Science and Innovation, Spain) and the FEDER fund (European Fund for Regional Development) was provided by grant UNGI08-4E-003. With the support of the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia and the Cofund programme of the Marie Curie Actions of the seventh R&D Framework Programme of the European Union

American Chemical Society (ACS)