Structure based peptide design, molecular dynamics and MM-PBSA studies for targeting C terminal dimerization of NFAT5 DNA binding domain.

摘要: NFAT5 as a transcription factor with an established role in osmotic stress response, has also been revealed to be active under numerous settings, including pathological conditions such diabetic microvascular complications, chronic arthritis and cancer. Despite these links, current strategies for downregulating activity only relies on indirect modulators, not directly targeting NFAT5, itself. With this study, through using computational approach, original peptide was explored target C terminal dimerization of RHR, located its DNA binding domain. At first, homodimeric RHR bound consensus used prediction preliminary sequence. Possible amino acid replacements were predicted optimization, which followed by addition cell penetrating These attempts yielded small library, further investigated affinities towards molecular docking, 50 ns 250 dynamics simulations, estimation MM-PBSA based relative free energies. Results indicated that after receiving mutations the sequence unique could region In conclusion, is first study presenting evidence identification novel capable dimerization. Besides, future implications observations discussed terms methodology possible applications.