Conservation and Network Analysis of the (4beta+alpha) Fold of the Immunoglobulin-Binding B1 Domain of Protein G to Elucidate the Key Determinants of Structure, Folding and Stability

摘要

Proteins fold from an ensemble of denatured states by a restriction of conformational space to form the initial native-like topology followed by further stabilizing secondary and tertiary interactions. It is believed that the formation of the initial native-like topology is guided by an evolutionarily conserved set of amino acids. Residues are typically conserved in a superfamily of proteins because they make critical interactions that are more important in maintaining the common fold. This could lead to residues clustering together in a hydrophobic core to stabilize the initial native-like topology [1,2]. This network of conserved amino acids has been the target of computational and experimental research which seeks to investigate the link between conserved amino acids and how they facilitate rapid and correct folding of a protein into its native state [3, 4, 5]. Using bioinformatics approaches we can determine and assess which amino acids are conserved for the fold of a protein. This type of analysis is highly useful and important in understanding the tertiary structure of proteins and becomes significantly more powerful when supported with experimental data. The application of network science has also become important in the study of protein structure and folding [2, 3, 6, 7, 8, 9].