Interaction between glyphosate and mitochondrial succinate dehydrogenase

Abstract

A recent study has evaluated the toxicity of the glyphosate-based herbicide, Roundup; the contents of the report evidences that the herbicide inhibits the mitochondrial succinate dehydrogenase activity. The present investigation, tries to prove the interaction of the active compound, glyphosate, with the succinate binding site of the enzyme, by using two-layer ONIOM calculations for structure optimization. In particular, the binding energy of the glyphosate-binding site complex model, in gas phase and polarized continuum medium in order to incorporate the protein environment, is calculated and compared it with a reference malonate-binding site complex model. The binding energy difference between these two model systems, ≈14kcalmol−1 at B3LYP/6-31+G(d) level of theory, supports the hypothesis of the interaction of glyphosate at the succinate binding site of the mitochondrial succinate dehydrogenase enzyme, verifying thus the experimental fact. Therefore, it is possible to conclude that glyphosate is harmful for the human health.