oa Editorial [Hot Topic: Protein Dynamics in Solution (Guest Editor: Hong-Yu Hu)]

It is well known that the primary sequence of a protein governs its three dimensional (3D) structure [1], on which, we suppose, molecular behavior and biological function of the protein are relied. It is more than 50 years since the first protein structure, hemoglobin, was solved in atomic resolution by x-ray crystallography [2]; people believe that the static structure of a protein is the fundamental for its unique function. With the advance of modern biophysical techniques, the efficiency for solving protein structures is accelerating dramatically to a speed beyond our expectation. Up to date, there are about 67, 000 structures deposited in the protein data bank (PDB) (http://www.rcsb.org/pdb). However, how a protein exerts its biological function is still a mystery to biologists. We have very limited information about the relationship between protein function and its structure, not even can we predict the function of a protein from its 3D structure. Protein structure is intrinsically dynamic in solution or solution-membrane interfaces [3]. For a protein, there are actually a large number of structures in solution [4]. We usually determine the time-averaged structure for a protein in solution by NMR [5] or a defined rigid structure in crystal by x-ray crystallography [2]. Simultaneously we often disregard the structural motion of a protein or its ensemble of conformations in solution, which may be critical to protein function and diversity. The dynamical structure is on a wide range of timescales [6], normally from pico- to kilo-seconds, reflecting respectively to the libration of chemical bonds, rotation of side-chains, fluctuation of backbones, reorientation of domains, and overall tumbling of global proteins. There is no doubt that protein structural motions relate to its biological function, such as protein-protein interaction and enzymatic catalysis [7]. This hot topic issue is aimed to provide a recent update on protein dynamics, which is the fundamental for protein functionality. With the advent of post-genomic era, a myriad of protein structures have been elucidated at atomic level, exploring their dynamical behaviors in solution is of great significance in understanding of the diverse functions of proteins [8]. The forthcoming review articles focus on the recent progresses in the dynamical aspects of proteins and their putative functional relationships including principles and methodology. Yan & Ji review the current research on the conformational dynamics and catalytic mechanism of 6-hydroxymethyl- 7,8-dihydropterin pyrophosphokinase, while Doucet discusses NMR relaxation dispersion method to characterize protein motion for enzyme engineering. The recently proposed models for the membrane-mediated protein interactions are reviewed by Armstrong et al. Many proteins are intrinsically flexible or partially disordered; the studies by Wang focus on the dynamics of amyloid β monomer by NMR techniques, while the flexible linkers of protein structures that may be pivotal to self-assembly of nanotubes are also reviewed by Buch et al. Some biophysical techniques have been developed to characterize the protein dynamics in different timescales. Among them, NMR spectroscopy is most versatile to study protein dynamics almost at all range of timescales. Sze & Lai review the recent progress in analyzing protein backbone dynamics by various NMR techniques, while Yang summarizes the methodology for side-chain dynamics of proteins by 13C NMR relaxation. Finally, I must reiterate that the fourth dimension, time, might be added to structural biology, and it is the time to explore the structure-dynamics-function relationships of proteins in all aspects of life sciences. I hope that the special issue will stimulate and inspire more structural biologists to be involved in this fascinating field of research, and will promote the research to expand our sights to the dynamical perspective of protein science [6,8,9].