Q Rev Biophys
2015[May]; 48
(2
): 117-77
PMID25850343
show ga
This is a tour of a physical chemist through 65 years of protein chemistry from
the time when emphasis was placed on the determination of the size and shape of
the protein molecule as a colloidal particle, with an early breakthrough by James
Sumner, followed by Linus Pauling and Fred Sanger, that a protein was a real
molecule, albeit a macromolecule. It deals with the recognition of the nature and
importance of hydrogen bonds and hydrophobic interactions in determining the
structure, properties, and biological function of proteins until the present
acquisition of an understanding of the structure, thermodynamics, and folding
pathways from a linear array of amino acids to a biological entity. Along the
way, with a combination of experiment and theoretical interpretation, a mechanism
was elucidated for the thrombin-induced conversion of fibrinogen to a fibrin
blood clot and for the oxidative-folding pathways of ribonuclease A. Before the
atomic structure of a protein molecule was determined by x-ray diffraction or
nuclear magnetic resonance spectroscopy, experimental studies of the fundamental
interactions underlying protein structure led to several distance constraints
which motivated the theoretical approach to determine protein structure, and
culminated in the Empirical Conformational Energy Program for Peptides (ECEPP),
an all-atom force field, with which the structures of fibrous collagen-like
proteins and the 46-residue globular staphylococcal protein A were determined. To
undertake the study of larger globular proteins, a physics-based coarse-grained
UNited-RESidue (UNRES) force field was developed, and applied to the
protein-folding problem in terms of structure, thermodynamics, dynamics, and
folding pathways. Initially, single-chain and, ultimately, multiple-chain
proteins were examined, and the methodology was extended to protein-protein
interactions and to nucleic acids and to protein-nucleic acid interactions. The
ultimate results led to an understanding of a variety of biological processes
underlying natural and disease phenomena.
free
free
free
