Computer modeling of protein tertiary structure and DNA binding energetics. I. Empirical free energy analysis of the engrailed Q50K variant-DNA complex and its mutants. II. The predicted structure of the adenovirus E4 orf6 protein by threading and comparative protein modeling.

摘要

Empirical free energy analyses and statistical potentials of mean force have been used by several groups to predict the strengths of protein-protein interactions and the tertiary structures of amino acid sequences, respectively. The engrailed Q50K variant is a classical homeodomain that binds its operator DNA molecule with little distortion of either the protein or the ligand, offering a ‘lock-and-key’ model of binding to a first approximation. This work consists, in part, of the first Gibbs free energy analysis of a protein-DNA complex, taking into consideration the considerable change in the DNA molecule's freedom of motion upon protein binding. The adenovirus E4 orf6 early gene product plays a crucial role in viral mRNA processing and export as well as oncogenic transformation of the infected cell. Although the protein's C-terminal most 226 residues are highly conserved across different adenovirus serotypes, it bears little homology with any protein of known structure. Using threading, or the application of statistical potentials of mean force, and comparative protein modeling, we predicted a tertiary structure for this protein. It is our hope that this structural information will aid in future research.