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The mechanistic insights into the oral pungency of capsaicin-related dietary components have been elucidated from the spatial structural perspectives by establishing statistically significant and highly predictive three-dimensional quantitative structure-property relationship models. Our results visualized the possible favorable and unfavorable steric and electrostatic interactions with the pungent receptors with the assistance of pharmacophore models, and revealed the suitable electronegative/positive or bulky substitutions in the vani