Molecular Dynamics Studies of Intrinsically Disordered Peptides and Proteins
Author | : Derya Meral |
Publisher | : |
Total Pages | : 298 |
Release | : 2015 |
ISBN-10 | : OCLC:978281093 |
ISBN-13 | : |
Rating | : 4/5 (93 Downloads) |
Book excerpt: A tremendous amount of evidence has accumulated in regards to the importance of intrinsically disordered proteins (IDPs) in the functioning of the cell and their role in human disease. However, understanding and modelling the physics of such proteins is one of the remaining challenges for the biophysics field. IDPs can present in a variety of forms, including flexible and extended structures, compact molten-globules, or mixtures of the two. Furthermore, many proteins which have regions with well-defined native states can have segments which are unfolded and disordered under physiological conditions. This thesis is an exploration of the physics of such IDPs, and the computational methodologies available for their study. The unfolded regions of intrinsically disordered proteins have long been described using the random coil model, which has been shown to successfully predict global properties such as the radius of gyration and intrinsic viscosities of IDPs and denatured proteins, alike. However, the two main axioms of the random coil model in regards to protein dynamics, (i) the ability of amino acid residues to sample the entire sterically allowed Ramachandran space, and (ii) the isolated pair hypothesis, which states that the conformations of residues are unaffected by nearest neighbour interactions, have been challenged through various lines of evidence. First, amino acid residues each have unique restrictions to their Ramachandran space. Second, many residues tend to have a strong bias for the pPII and beta-strand conformations. Third, the conformations of residues in protein sequences are strongly affected by nearest neighbour interactions. Part of this thesis explores the underlying causes of the distinct Ramachandran spaces of amino acid residues. In a recent experimental study of the thermodynamics of the pPII-beta equilibria of amino acid residues in GxG host-guest peptide systems (G: glycine, x: guest residue), a nearly exact enthalpy-entropy compensation at