An Amber Force Field for S-Nitrosoethanethiol That Is Transferable to S-Nitrosocysteine

Abstract

Protein S-nitrosation is common in cells under nitrosative stress. In order to model proteins with S-nitrosocysteine (CysSNO) residues, we first developed an Amber force field for S-nitrosoethanethiol (EtSNO) and then transferred it to CysSNO. Partial atomic charges for EtSNO and CysSNO were obtained by a restrained electrostatic potential approach to be compatible with the Amber-99 force field. The force field parameters for bonds and angles in EtSNO were obtained from a generalized Amber force field (GAFF) by running the Antechamber module of the Amber software package. The GAFF parameters for the CC-SN and CS-NO dihedrals were not accurate and thus determined anew. The CC-SN and CS-NO torsional energy profiles of EtSNO were calculated quantum mechanically at the level of B3LYP/cc-pVTZ//HF/6-31G*. Torsional force constants were obtained by fitting the theoretical torsional energies with those obtained from molecular mechanics energy minimization. These parameters for EtSNO reproduced, to a reasonable accuracy, the corresponding torsional energy profiles of the capped tripeptide ACE-CysSNO-NME as well as their structures obtained from quantum mechanical geometry optimization. A molecular dynamics simulation of myoglobin with a CysSNO residue produced a well-behaved trajectory demonstrating that the parameters may be used in modeling other S-nitrosated proteins.

The Radical Ion Chemistry of S-Nitrosylated Peptides

“…The S-nitrosylation amino acids were added manually using previously calculated parameters [24]. Peptides underwent 500 cycles of steepest descent followed by 500 of conjugant gradient minimization followed by heating in a stepwise manner from 0 K up to 325 K. Each heating step consisted of 10,000 steps of 0.5 fs each (nstlim010000, dt00.0005), using a Langevin thermostat (ntt03, gamma_ln01.0) with no interacting solvent (igb00).…”

PTM‐Psi: A python package to facilitate the computational investigation of post‐translational modification on protein structures and their impacts on dynamics and functions

“…Table 3 compares equilibrium bond distances, , and harmonic bond stretching force constants, , or the same three methodologies as those used for determining charges in Table 2. Han's methodology (Han, 2010), which optimizes the structures at the Hartree–Fock level, gives a rather short SN equilibrium bond distance but an NO distance of about the same magnitude as the MP2 calculations of Croitoru et al (2021). In contrast, our calculations with the r 2 SCAN density functional approximation (DFA) enlarge the SN and shorten the NO bonds, indicating a less conjugated character.…”

“…Since we aimed to obtain parameters that were compatible with the FF99SB force field, the PTM‐Psi charges were calculated using the N ‐acetyl‐( S ‐nitrosocysteinyl)‐ N′ ‐methylamine (ACE‐SNC‐NME) dipeptide in the gas phase. The partial charges obtained by Han (Han, 2010 ) for the FF99SB force field were derived using a similar methodology on the S ‐nitrosoethanethiol model fragment. Han's methodology also differs from ours in that the geometry optimizations were calculated with a different QM setup.…”