Protein-Protein Interaction Prediction Based on Spectral Radius and General Regression Neural Network.

Protein-protein interaction (PPI) not only plays a critical role in cell life activities, but also plays an important role in discovering the mechanism of biological activity, protein function, and disease states. Developing computational methods is of great significance for PPIs prediction since experimental methods are time-consuming and laborious. In this paper, we proposed a PPI prediction algorithm called GRNN-PPI only using the amino acid sequence information based on general regression neural network and two feature extraction methods. Specifically, we designed a new feature extraction method named Mutation Spectral Radius (MSR) to extract evolutionary information by the BLOSUM62 matrix. Meanwhile, we integrated another feature extraction method, autocorrelation description, which can completely extract information on physicochemical properties and protein sequences. The principal component analysis was applied to eliminate noise, and the general regression neural network was adopted as a classifier. The prediction accuracy of the yeast, human, and Helicobacter pylori1 (H. pylori1) data sets were 97.47%, 99.63%, and 99.97%, respectively. In addition, we also conducted experiments on two important PPI networks and six independent data sets. All results were significantly higher than some state-of-the-art methods used for comparison, showing that our method is feasible and robust.

Rosetta comparative modeling for library design: Engineering alternative inducer specificity in a transcription factor.

Structure-based rational mutagenesis for engineering protein functionality has been limited by the scarcity and difficulty of obtaining crystal structures of desired proteins. On the other hand, when high-throughput selection is possible, directed evolution-based approaches for gaining protein functionalities have been random and fortuitous with limited rationalization. We combine comparative modeling of dimer structures, ab initio loop reconstruction, and ligand docking to select positions for mutagenesis to create a library focused on the ligand-contacting residues. The rationally reduced library requirement enabled conservative control of the substitutions by oligonucleotide synthesis and bounding its size within practical transformation efficiencies (∼ 10(7) variants). This rational approach was successfully applied on an inducer-binding domain of an Acinetobacter transcription factor (TF), pobR, which shows high specificity for natural effector molecule, 4-hydroxy benzoate (4HB), but no native response to 3,4-dihydroxy benzoate (34DHB). Selection for mutants with high transcriptional induction by 34DHB was carried out at the single-cell level under flow cytometry (via green fluorescent protein expression under the control of pobR promoter). Critically, this selection protocol allows both selection for induction and rejection of constitutively active mutants. In addition to gain-of-function for 34DHB induction, the selected mutants also showed enhanced sensitivity and response for 4HB (native inducer) while no sensitivity was observed for a non-targeted but chemically similar molecule, 2-hydroxy benzoate (2HB). This is unique application of the Rosetta modeling protocols for library design to engineer a TF. Our approach extends applicability of the Rosetta redesign protocol into regimes without a priori precision structural information.

Novel Method of 3-Dimensional Graphical Representation for Proteins and Its Application.

In this article, we propose a 3-dimensional graphical representation of protein sequences based on 10 physicochemical properties of 20 amino acids and the BLOSUM62 matrix. It contains evolutionary information and provides intuitive visualization. To further analyze the similarity of proteins, we extract a specific vector from the graphical representation curve. The vector is used to calculate the similarity distance between 2 protein sequences. To prove the effectiveness of our approach, we apply it to 3 real data sets. The results are consistent with the known evolution fact and show that our method is effective in phylogenetic analysis.