All-atom molecular dynamics simulations of phenylalanine-4-hydroxylase (PAH) tetramer to investigate the impact of two novel heterozygous mutations, p.Y198N and p.Y204F, observed in a classical phenylketonuria patient

<p>Phenylalanine-4-hydroxylase (PAH) tetramer system (Robetta modelling to complete the structure&nbsp;with template&nbsp;PDB ID: 6hyc)&nbsp;with parametrised&nbsp;BH₄ ligand (parameters are available in the dataset) and&nbsp;Fe(II) metal ions in a TIP3P water box ionised with 0.15 M KCl were presented as wild-type and carrying two novel mutations as&nbsp;Y198N on dimeric chains A and B, and&nbsp;Y204F on dimeric chains C and D. In addition,&nbsp;E353 and E422 are&nbsp;protonated as predicted by PROPKA.&nbsp;BH₄&nbsp;molecule parametrization&nbsp;was performed&nbsp;by using GAFF, Antechamber and &ldquo;amb2chm_par.py&rdquo; program of Amber2018.</p> <p>5,000-step minimization and 1 ns equilibration were performed by fixing the protein to relax the system. Then, another 5,000-step minimization and 1 ns equilibration were performed without any constraints, except the SHAKE algorithm&nbsp;on water molecules, to relax the protein and system. The production simulations were performed along 100 ns trajectory at 310 K collected under NpT ensemble.</p> <p>All system preparation and&nbsp;simulation details for this dataset is available with the related background, results and conclusions&nbsp;in the following article:</p> <p>Tolga Aslan, Aslı Yenenler-Kutlu, Umut Gerlevik, Ayşe &Ccedil;iğdem Aktuğlu Zeybek, Ertuğrul Kıykım, Osman Uğur Sezerman &amp; Necla Birgul Iyison&nbsp;(2021)&nbsp;Identifying and elucidating the roles of Y198N and Y204F mutations in the PAH enzyme through molecular dynamic simulations,&nbsp;Journal of Biomolecular Structure and Dynamics,&nbsp;DOI:&nbsp;<a href="https://doi.org/10.1080/07391102.2021.1921619">10.1080/07391102.2021.1921619</a></p>