In the present work, the reaction mechanisms for the newly characterized single and double NOS bonds in proteins are computationally investigated. More than 30 intermediates were considered for oxidation pathways involving different ROS. The results indicate that the sulfinic acid is thermodynamically very favoured and so its formation would lead the reaction to a dead end. An intermediate with a lower sulphur oxidation state is required for the formation of the NOS bond. The sulfenic acid is shown to be a suitable candidate but its overoxidation could potentially lead to the formation of the sulfinic acid. In this vein, the thio-(hydro)peroxy acid is shown to be another potential oxidation intermediate which allows the formation of the NOS bond. Several different oxidant agents are considered and it is shown that radical derivatives of H 2 O 2 are readibly able to form this intermediate. Redox potentials clearly show that the process should be reversible, which is further supported by the computed activation barriers.