AMBER parameters and topology data of 2-pentylpyrrole adduct of arginine with 4-hydroxy-2-nonenal

The data described here supports a part of the research article “Effect of 4‑HNE Modification on ZU5-ANK Domain and the Formation of Their Complex with β‑Spectrin: A Molecular Dynamics Simulation Study” [1]. Dataset on Gaff force field parameters of AMBER is provided for the non-standard arginine resulting of reaction with 4-hydroxy-2-nonenal (4-HNE), the major secondary product of lipids peroxidation. Arg-HNE 2-pentilpyrrole adduct is part of the 4-hydroxyalkenals described in various physiopathological disorders related to increased oxidative stress. Data include a framework for derivation of missing bonds, angles and dihedral parameters for modified arginine, alongside optimized partial charges derived with Restrained Electrostatic Potential (RESP) method and the new force field parameters obtained by quantum mechanicals methods (QM) using Hartree-Fock (HF)/6 - 31G** level of theory. Benchmark as a graphics tutorial summary steps to obtained new parameters and the validation of non-standard amino acids is presented. The new residue constructed is put available to the scientific community to perform molecular dynamics simulations of modified 4-HNE proteins on arginine residue and complete the set of data parameters for nucleophilic residues with this reactive aldehyde ADDIN EN.CITE ADDIN EN.CITE.DATA [2]. Data that could be used for the researchers interested in the role of protein oxidation as mediator in cellular pathophysiological.


a b s t r a c t
The data described here supports a part of the research article "Effect of 4-HNE Modification on ZU5-ANK Domain and the Formation of Their Complex with b-Spectrin: A Molecular Dynamics Simulation Study" [1]. Dataset on Gaff force field parameters of AMBER is provided for the non-standard arginine resulting of reaction with 4-hydroxy-2-nonenal (4-HNE), the major secondary product of lipids peroxidation. Arg-HNE 2-pentilpyrrole adduct is part of the 4-hydroxyalkenals described in various physiopathological disorders related to increased oxidative stress. Data include a framework for derivation of missing bonds, angles and dihedral parameters for modified arginine, alongside optimized partial charges derived with Restrained Electrostatic Potential (RESP) method and the new force field parameters obtained by quantum mechanicals methods (QM) using Hartree-Fock (HF)/6 -31G** level of theory. Benchmark as a graphics tutorial summary steps to obtained new parameters and the validation of non-standard amino acids is presented. The new residue constructed is put available to the scientific community to perform molecular dynamics simulations of modified 4-HNE proteins on arginine residue and complete the set of data parameters for nucleophilic residues with this reactive aldehyde ADDIN EN.CITE ADDIN EN.CITE.DATA [2]. Data that could be used for the researchers interested in the role of protein oxidation as mediator in cellular pathophysiological.
© 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

Data Description
The dataset included in this article consists of 3 Tables and 3 figures. In the Table 1 the dataset of partial charges assigned to Arg-HNE is shown. Table 2 contains the dataset with the information of new obtained parameters listed as coordinates file for 4HNE-arginine pyrrole adduct; while in Table 3 is summarized the comparative data of selected bond distances and angles used in the validation step. In Fig. 1, the workflow for preparing parameter files for 2-pentylpyrrole adduct is described; while, the optimized structure for the new non-standard residue obtained with theory level HF/6-31G** is presented in Fig. 2. The running average of all atoms RMSD for non-modified and 4-HNE-modified arginine is showed in Fig. 3

Parameterization
Dataset of Gaff force field parameters were established for the non-standard amino acid Arg-HNE and its use for molecular dynamics simulations of proteins [1]. In the Fig. 1 is presented the framework for derivation of missing bond, angle and dihedral parameters. First, non-standard amino acid was constructed with GaussView 5, followed by full geometry optimization of the new structure using the Hartree-Fock level (HF/6 -31G**) [2,3]. Next, assignment of charges, missing bonds, angles, and   dihedral angles parameters were constructed with the antechamber and leap programs as included in AmberTools 16 [4]. Then, charges (Step 4) of the optimized structures were calculated using RESP method [5] and the partial charges assigned to individual atoms are listed in the Table 1. Missing bonds, angles, and dihedral parameters of 4-HNE modified arginine was established by homology, matching atom types automatically from the Gaff force field and using parmchk to generate the required force constants [4]. Dataset of new parameters assigned for the 2-pentylpyrrole adduct were consigned in frcmod files and they are summarized below in Table 2. Next, coordinate and topology files were created for each non-standard amino acid with the program leap.
This Arg-HNE was replaced on the proteins and the lacking parameters in frcmod files corresponding to peptide bonds, angle and torsions between the non-standard amino acids and the end nitro-terminus and the end carboxyl terminus of the nearby amino acids on proteins, were calculated using the program parmcal of Antechamber package. The improved frcmod file was loaded into tleap program from AmberTools16 to generate the libraries files (type lib files).
Finally, the optimized structure of 4HNE-arginine pyrrole adduct is showed in Fig. 2; whereas the new improved parameters were included into Table 2. There, bond parameters values are expressed as bond constants (kr) in kcal·mol À1 Å À2 ; distance at equilibrium (req) in Å; angle constant (kq) in  kcal·mol À1 deg À2 ; angle at equilibrium (Qeq) in degrees, dihedrals constants (Vn/2) in kcal/mol and dihedrals constants angles (j) in degrees.
From these datasets, the topology and coordinate of modified proteins were obtained. Hence, the applicability of the newly derived MM parameter, they were subsequently employed in 1 ms MD simulations of Arg-HNE as an amino acids treated following the methodology described by Refs. [1,6].

Validation
To test the generated structures from the modified arginine we performed MD simulations as described above using only the modified structure and compared selected bond distances and angles with structures obtained from DFT level of theory m062x/631g (d) ( Table 3) [1]. Overall, good agreement between the data from high-level QM calculations and the generated AMBER structures were seen. Distance average error is in~0.02 Å whereas angle error is within~4 and 3 Å.
Data from the single modified amino acids were extracted from a 1 ms MD simulation using the same protocols describe before, comparisons were calculated using the DFT level of theory m062x and a basis set 6e31g.

Analysis of molecular dynamics trajectories of non-standard vs. standard amino acids
All atom root means square deviation analysis for unmodified and modified amino acids is presented in Fig. 3. Distance found in RMSD analysis for unmodified arginine was~1,5 Ålower than that found for ARG-HNE, which was~2.5 Å (Fig. 3). Differences observed fall into a range of 1 Å for RSMD comparisons among modified/unmodified arginine indicating that 4-HNE do not induce dramatically structural changes.