Efeitos da fosforilação e o mecanismo molecular com o hDAT e o transporte de dopamina (absorção e efluxo).
hDAT plays an important role in the modulation of the dopamine Influx /Efflux and it may be involved in the mechanism of certain neurodegenerative diseases such as Parkinson's disease. Macromolecules adopt many conformations in solution dependent on their structure and shape, which determine their dynamics and function. Considering this context, several studies have reported metasatestates for Dopamine Transport: outward-facing open state (OFo), the outward-facing closed state (OFc), the holo-occluded state closed (holo), and the inward-facing open state (IFo). Experimental assays showed that different phosphorylation conditions can affect the rate of dopamine absorption. This work presents a protocol using hybrid simulation methods to study the conformational dynamics and stability of these metasates of hDat under phosphorylation conditions focusing on understanding the relationship between: metastases, dopamine transport and these post-transcriptional modification. We present here the results obtained with our hybrid simulations to correlate its phosphorylation with the movements and formation of metastates described in the literature. We show which movements promote which of the states, the transitions between them, and a free energy analysis considering four different phosphorylation conditions of hDAT as described in the literature.