Thats a unique idea.You should consider the following idea to enhance your idea so that it would impact uniquely: The causative agent of African sleeping sickness, Trypanosoma brucei, undergoes an unusual mitochondrial RNA editing process that is essential for its survival. RNA editing terminal uridylyl transferase 2 of T. brucei (TbRET2) is an indispensable component of the editosome machinery that performs this editing. TbRET2 is required to maintain the vitality of both the insect and bloodstream forms of the parasite, and, with its high-resolution crystal structure, it poses as a promising pharmaceutical target. Neither the exclusive requirement of UTP for catalysis, nor the RNA primer preference of TbRET2 is ll understood. Using all-atom explicitly solvated molecular dynamics (MD) simulations,  investigated the effect of UTP binding on TbRET2 structure and dynamics, as ll as the determinants governing TbRET2’s exclusive UTP preference. Through our investigations of various nucleoside triphosphate substrates (NTPs),  show that UTP pre-organizes the binding site through an extensive water-mediated H-bonding network, bringing Glu424 and Arg144 sidechains to an optimum position for RNA primer binding. In contrast, CTP and ATP cannot achieve this pre-organization and thus preclude productive RNA primer binding. Additionally,  have located ligand-binding “hot spots” of TbRET2 based on the MD conformational ensembles and computational fragment mapping. TbRET2 reveals different binding pockets in the apo and UTP-bound MD simulations, which could be targeted for inhibitor design.
['Özlem Demir', 'Rommie E. Amaro']
I am writing a research paper on a idea Elements of nucleotide specificity in the Trypanosoma brucei mitochondrial RNA editing enzyme RET2.
[{"from": "human", "value": "I am writing a research paper on a idea Elements of nucleotide specificity in the Trypanosoma brucei mitochondrial RNA editing enzyme RET2."}, {"from": "gpt", "value": "Thats a unique idea.You should consider the following idea to enhance your idea so that it would impact uniquely: The causative agent of African sleeping sickness, Trypanosoma brucei, undergoes an unusual mitochondrial RNA editing process that is essential for its survival. RNA editing terminal uridylyl transferase 2 of T. brucei (TbRET2) is an indispensable component of the editosome machinery that performs this editing. TbRET2 is required to maintain the vitality of both the insect and bloodstream forms of the parasite, and, with its high-resolution crystal structure, it poses as a promising pharmaceutical target. Neither the exclusive requirement of UTP for catalysis, nor the RNA primer preference of TbRET2 is ll understood. Using all-atom explicitly solvated molecular dynamics (MD) simulations,  investigated the effect of UTP binding on TbRET2 structure and dynamics, as ll as the determinants governing TbRET2\u2019s exclusive UTP preference. Through our investigations of various nucleoside triphosphate substrates (NTPs),  show that UTP pre-organizes the binding site through an extensive water-mediated H-bonding network, bringing Glu424 and Arg144 sidechains to an optimum position for RNA primer binding. In contrast, CTP and ATP cannot achieve this pre-organization and thus preclude productive RNA primer binding. Additionally,  have located ligand-binding \u201chot spots\u201d of TbRET2 based on the MD conformational ensembles and computational fragment mapping. TbRET2 reveals different binding pockets in the apo and UTP-bound MD simulations, which could be targeted for inhibitor design."}]