Virtual Screening of Natural Products, Molecular Docking and Dynamics Simulations on M. tuberculosis S-adenosyl-L-homocysteine Hydrolase

摘要

The activated methyl cycle of Mycobacterium tuberculosis (Mtb)is responsible for the regeneration of S-adenosyl methionine (SAM) from S-adenosyl-L-homocysteine (SAH). Inhibition of the key enzymes in this transformation may lead to accumulation of SAH and depletion of SAM in the Mtb cell. This has detrimental effects onthe bacterium's cellular processes. Virtual screening of natural products from the Philippines and those in Ambinter database against S-adenosyl-L-homocysteine hydrolase (SAHH) yielded the tautomer of the molecule, methyl 4-({2-[(4-hydroxy-2-oxo-1,2-dihydro-3-quinolinyl)carbonyl]hydrazino}sulfonyl)phenylcarbamate, which displays better binding energy (-307.64 kcal/mol) than the substrate, SAH (-270.601 kcal/mol). Molecular dynamics simulations at body temperature indicated that the hit-SAHH complex is more stable than the enzyme-substrate complex.