QSAR Study of Interaction between Estrogen Derivatives and Receptor Amino Acids using Softness Parameters

Four sets of estrogen derivatives have been studied in respect of their interaction with receptor amino acids. The estrogen derivatives are divided into four sets on the basis of the positions of the substituents. The first set is substituted at the position 16, second at 17, third at 11, 16, 17 and fourth at 2, 4, 7, 11, 17. The receptor amino acids are lysine, tyrosine, cysteine and histidine. The softness parameter n E at different sites of estrogen and softness parameter ‡ m E at different sites of lysine, tyrosine, cysteine and histidine has been evaluated with the help of PM3 calculation. The highest value of n E of estrogen and highest value of ‡ m E of amino acids have been chosen. The difference between the values of n E and ‡ m E have been derived and are shown as ‡ nm ΔE . The reciprocal of ‡ nm ΔE , ‡ n E and ‡ m E values have been used as descriptors for development of QSAR models. QSAR models of all the four sets of estrogen derivatives have been developed which show high degree of predictive power as the regression coefficient values are about 0.90. The best descriptor for all the four sets of estrogen derivatives can be supposed to be 1/H nm ΔE , where H ‡ nm ΔE denotes the difference between acidic softness values n E of derivatives of estrogen and basic softness values ‡ m E of histidine. The quality of interaction of estrogen derivatives with different amino acids has also been obtained by nm ΔE values.