scoring function to predict solubility mutagenesis得分函数预测溶解度诱变.pdfVIP

Scoring function to predict solubility mutagenesis Tian et al. Tian et al. Algorithms for Molecular Biology 2010, 5:33 /content/5/1/33 (7 October 2010) Tian et al. Algorithms for Molecular Biology 2010, 5:33 /content/5/1/33 RESEARCH Open Access Scoring function to predict solubility mutagenesis 1 2 1* Ye Tian , Christopher Deutsch , Bala Krishnamoorthy Abstract Background: Mutagenesis is commonly used to engineer proteins with desirable properties not present in the wild type (WT) protein, such as increased or decreased stability, reactivity, or solubility. Experimentalists often have to choose a small subset of mutations from a large number of candidates to obtain the desired change, and computational techniques are invaluable to make the choices. While several such methods have been proposed to predict stability and reactivity mutagenesis, solubility has not received much attention. Results: We use concepts from computational geometry to define a three body scoring function that predicts the change in protein solubility due to mutations. The scoring function captures both sequence and structure information. By exploring the literature, we have assembled a substantial database of 137 single- and multiple- point solubility mutations. Our database is the largest such collection with structural information known so far. We optimize the scoring function using linear programming (LP) methods to derive its weights based on training. Starting with default values of 1, we find weights in the range [0,2] so that predictions of increase or decrease in solubility are optimized. We compare the LP m