High performance global exploration of isomers and isomerization channels on the quantum chemical potential energy surface (PES) is performed for H5C2NO2 by using the scaled hypersphere search‐anharmonic downward distortion following (SHS‐ADDF) method. A multi‐node operation, NeoGRRM, has achieved high performance exploration calculations for the large system by submitting SHS‐ADDF sub‐jobs into many cores in parallel and unifying the results of sub‐jobs into the total lists of the main‐job. Global exploration of equilibrium (EQ) and transition‐state structures at the level of B3LYP/6‐31G(d) gave 3210 EQs and 23278 TSs. Nine compounds were found in the low energy regions of 0–100 kJ/mol; the lowest energy compound is N‐methylcarbamic acid, the second is methyl carbamate, and the third is glycine (the most fundamental amino acid). Interconversion pathways between the conformers of each of the low energy compounds were surveyed. Isomerization channels around glycine were explored in detail. The lowest energy barriers around some of the EQs turned to be negative after zero‐point energy corrections. This indicates that those structures cannot exist as independent structures because they spontaneously collapse into more stable structures. The global PES search showed various interesting dissociating channels which indicate synthon reaction pathways in the reverse directions.