In silico method to design a new protein that exhibits higher thermostability and functional specificity

Abstract

Protein engineering is the application of science, mathematics, and economics to the process of developing useful or valuable proteins. It is a young discipline, with much research currently taking place into the understanding of protein folding and protein recognition for protein design principles. Computational protein design algorithms seek to identify amino acid sequences that have low energies for target structures. While the sequence-conformation space that needs to be searched is large, the most challenging requirement for computational protein design is a fast, yet accurate, energy function that can distinguish optimal sequences from similar sub-optimal ones. Using computational methods, a protein with a novel fold has been designed, as well as sensors for un-natural molecules. Here we propose a new computational method named TargetStar as $\It{in silico}$ system for the protein design. Then we validate the prediction accuracy of the TargetStar through the statistical analysis on the results of TargetStar analysis. Finally we apply our TargetStar to the design of a new protein that gives higher thermostability and functional specificity. The proposed system TargetStar is an $\It{in silico}$ system that predicts the thermal stability of an input amino acid sequence. TargetStar defines five energy functions and their energy parameters that can assess the fitness of a given amino acid sequence to the native structure against decoy (non-native) structures. TargetStar views a protein as a system. To predict the thermal stability of a protein sequence, TargetStar implements an approximate partition function of a protein (i.e. a system) from the concept of partition function in statistical physics using the defined energy functions, and it calculates specific heat using the approximate partition function. All the macroscopic properties of a system such as the energy and specific heat can be calculated in terms of a partition function. To validate t...