This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The recognition of specific DNA-binding sites by transcription factors is a critical yet poorly understood step in the control of gene regulation. Functional specificity of a Hox Protein has been reported to occur by recognition of DNA minor groove structure containing A-tract sequences AGATTAATCG and TCATTTAT.(1) We propose computational studies on theses DNA duplexes, based on crystallographic data, to study the effects of sequence on the geometry of the minor groove. The proposed study will use state of the art Molecular Dynamics Simulation Methods, the PARMBSC0 version of the Amber forcefield for nucleic acids, which has been recently reported in the literature and has improvements related to the backbone alpha/gamma transitions. This study may shed light on the mechanism by which Hox proteins recognize specific binding sites when presented with the correct DNA sequence that may confer specificity by recognizing a sequence-dependent DNA structure. 1. Functional Specificity of a Hox Protein Mediated by the Recognition of Minor Groove Structure. Cell, 131, 530-543, November 2, 2007.
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