This study was carried out to develop a quantitative structure-activity relationship (QSAR) model of the biological activity of indole glyoxamide derivatives as inhibitor of the interaction between human immunodeficiency. the gp120 glycoprotein of the virus (HIV) and the CD4 receptors of the host cell. In the present study, forty different compounds were selected as the sample set. Combinations of multiple linear regressions (MLR), genetic algorithms (GA) and artificial neural networks (ANN) were then used to construct the QSAR models. These models were also used to nonlinearly select the most effective descriptor subsets in a cross-validation procedure for nonlinear logarithmic prediction (1/EC50). The results obtained with GA-ANN were compared to the MLR-MLR and MLR-ANN models. The resulting models showed high prediction ability with root mean square error (RMSE) of 0.99, 0.91, and 0.67 for the MLR, MLR-ANN, and GA-ANN models, respectively (N=40). Keywords: Genetic algorithm; artificial neural network; multiple linear regressions; HIV; Quantitative structure – Activity relationship;1. IntroductionThe process of entry of human immunodeficiency virus-1 (HIV-1) into host cells offers considerable potential for therapeutic intervention, with viral entry proceeding through several sequential steps involving attachment, binding to coreceptors and fusion (8, 13). The first step in virus entry into the host cell is accomplished by binding of the viral envelope glycoprotein complex gp160 to the cellular receptor CD4. This attachment is followed by conformational changes to the outer glycoprotein portion gp160, gp120, which facilitate the second step involving binding to a cellular co-receptor, usually the chemokine receptor...... middle of paper ..... .odeschini R, Pavan M et al (2002) J. Chem. Inf. Calculate. Sci. 42, 693-705.15. Gramatica P, Consonni V, Todeschini R (1999) Chemosphere 38, 1371-1378.16. Gramatica P, Corradi M, Consonni V. (2000) Chemosphere 41, 763-777.17. Fatemi MH & Gharaghani S (2007) Bioorganic and medicinal chemistry. 15, 7746-7754.18. Nirouei M, Abdolmaleki P, Tavakoli A et al (2008) Proceedings of the 2nd International Conference on Electrical Engineering Design and Technology, Hammamat, Tunisia.19. Zhang P, Verma B, Kumar K (2005) Letter pattern recognition. 26, 909-919.20. Sadat Hayatshahi SH, Abdolmaleki P, Safarian S et al (2005) Biochem. Biophysics. Res. Common. 338, 1137-1142.21. Weekes D, Fogel GB (2003) BioSystems. 72, 149-158.22. Cheng Z, Zhang Y, Zhou C et al (2010) International Journal of Digital Content Technology and its Applications, Vol.. 4, 2 , 109-121.