Title:

Molecular Simulation Studies of Protein Interactions Involved in Aging: Investigating the Recruitment Mechanism of PRC2 and DNMT3A

The degradation of the epigenome has been identified as one of the primary causes of aging [1]. Two proteins which maintain the epigenome, DNA Methyltransferase 3A (DNMT3A) and the Polycomb Repressive Complex 2 (PRC2), have been experimentally determined to recruit each other throughout the genome to catalyze epigenetic modification at specific sites, but the exact mechanism of this interaction remains unclear [3]. The primary objective of this project was to computationally investigate the recruitment interaction between DNMT3A and PRC2 using docking and molecular dynamics simulations. Through pursuing this objective it was hoped a broader understanding of epigenetic modifier protein recruitment could be gained, and conversely how the decay of these proteins contributes to aging. Multiple computational models of PRC2 and DNMT3A were developed and simulated interacting with each other. Based on the results of these simulations, in addition to a broader literature review, a hypothesis was developed that the ADD domain of DNMT3A and the SANT I domain of PRC2 are prominently involved in the recruitment interaction between DNMT3A and PRC2.

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