Abstract
Targeting the precursors of trimethylamine-N-oxide(TMAO), such as choline, betaine, and enzymes produced by the FMO3 gene, through natural compounds may reduce risk factors such as cardiovascular and metabolic diseases. Protein precursors involved in high TMAO level production include cntA, CUTC, and FMO3. Manalagi apple (Malus sylvestris) isrich in bioactive compounds, including pectin, phloretin, and chlorogenic acid,with potential health benefits,and would affect the decreasing production of TMAO by inhibiting some protein precursors. This researchaims to investigate the potential of three small molecules in itas a dietary sourcecandidate and drug candidate that could mitigate the risk of TMAO-related diseases based on theirinteraction and binding affinity through an in-silicostudy.The methodsinclude theprediction of protein and small-molecule structures, including FTIR,molecular docking, and analysis ofsmall-molecule bioavailability.Pectin is considered the top candidate compared to phloretin and chlorogenic acid based on its high binding affinity to interactwith CUTC, cntA, and FMO3(-10.2, -8.6, and -9.1 kcal/mol, respectively). Phloretin isa promising compound for drug development based on its binding site to interact with more residues and bonds, its bioavailabilitywith a drug likeness score of 0.55,and high gastrointestinal absorption.