Modeling Physicochemical Properties and Activity of Aspartyl Proteinases Based on Amino Acid Composition

Abstract

A data set containing physicochemical properties and enzymatic activity measurements of aspartyl proteinases was employed for quantitative structure-property relationship (QSPR) and quantitative structure-activity relationship (QSAR) modeling based on either three or five amino acid principal property sums. All but one of the models based on five principal properties were stronger than those based on three properties. Models of zeta potential (R2 = 0.846), circular dichroism (R2 = 0.638), Bigelow average hydrophobicity (R2 = 0.692), accessible surface area (R2 = 0.897), and two dye-based assessments of hydrophobicity (R2 = 0.581 and 0.595) were constructed. Model quality was evaluated by cross-validation and permutation. The amino acids most influential for each modeled property were identified. It is clearly possible to model physicochemical properties of proteins as a function of amino acid principal property sums. Surprisingly, it was also possible to model an enzyme activity ratio (milk clotting/proteolytic activity) in the same manner (R2 = 0.699).