QSAR Models for the Prediction of Binding Affinities to Human Serum Albumin Using the Heuristic Method and a Support Vector Machine

• Published in: Journal of Chemical Information and Computer Sciences 2004-09, Vol.44 (5), p.1693-1700
• Main Authors: Xue, C. X, Zhang, R. S, Liu, H. X, Yao, X. J, Liu, M. C, Hu, Z. D, Fan, B. T
• Format: Article
• Language: English
• Subjects: Circulatory system; Computer science; Humans; Mathematical models; Models, Chemical; Pharmaceuticals; Protein Binding; Quantitative Structure-Activity Relationship; Serum Albumin - metabolism
• ISSN: 0095-2338; 1549-9596; 1549-960X
• DOI: 10.1021/ci049820b

The binding affinities to human serum albumin for 94 diverse drugs and drug-like compounds were modeled with the descriptors calculated from the molecular structure alone using a quantitative structure−activity relationship (QSAR) technique. The heuristic method (HM) and support vector machine (SVM) were utilized to construct the linear and nonlinear prediction models, leading to a good correlation coefficient (R 2) of 0.86 and 0.94 and root-mean-square errors (rms) of 0.212 and 0.134 albumin drug binding affinity units, respectively. Furthermore, the models were evaluated by a 10 compound external test set, yielding R 2 of 0.71 and 0.89 and rms error of 0.430 and 0.222. The specific information described by the heuristic linear model could give some insights into the factors that are likely to govern the binding affinity of the compounds and be used as an aid to the drug design process; however, the prediction results of the nonlinear SVM model seem to be better than that of the HM.