A ribosome is a large RNA-protein machine that catalyzes protein synthesis. RNA plays a crucial role in catalyzing peptide bond formation. In this Letter, we focus on the catalytic role of the A76 2'-OH of the P site in tRNA. Three possible reaction schemes were compared using the same reaction model and theoretical level. By comparison of the potential energy surface and optimized geometries of transition states, a new favorable reaction pathway is shown. The activation energy is 24.0 kcal/mol. This work will provide a foundation for further theoretical and experimental study of ribosome mechanisms. (C) 2010 Elsevier B. V. All rights reserved.