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

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

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.