Studyng the dynamics of binding of CREB to CBP and p53

ITHURALDE, RE; TURJANSKI, AG

Salta

Congreso; 3rd Latin American Protein Society Meetting; 2010

Latin American Protein Society

The PNDs are a group of proteins that lack a defined three-dimensional structure in solution but which can acquire a specific conformation when they interact with other biomacromolecules such as proteins or DNA. Given the recent interest in these proteins and considering that its experimental characterization is extremely difficult, computational simulation methods have emerged as an alternative to answer basic questions about its functions. We will use classical molecular dynamics techniques with coarse-grained and "all atom" potentials to study the binding of a group of transcription factors natively unstructured to their transcription co-factors. In particular , we will study the binding of transcription factors CREB and p53 to the cofactor CBP. Understanding the mechanisms of recognition of transcription factors is crucial to understanding their role and develop strategies to avoid its aberrant activation. In summary we intend to develop the following: To analyze the different mechanisms of binding to biomacromolecules PNDS Characterizing the binding of CREB and p53 to CBP Study how phosphorilation of CREB and p53 affects the kinetics of binding to CBP (in specific relation to kon and koff). Recognize if the mechanism is binding-folding,  folding-binding or an intermediate between both.