Abstract
Protein structural biology came a long way since the determination of the first three-dimensional structure of myoglobin about six decades ago. Across this period, X-ray crystallography was the most important experimental method for gaining atomic-resolution insight into protein structures. However, as the role of dynamics gained importance in the function of proteins, the limitations of X-ray crystallography in not being able to capture dynamics came to the forefront. Computational methods proved to be immensely successful in understanding protein dynamics in solution, and they continue to improve in terms of both the scale and the types of systems that can be studied. In this review, we briefly discuss the limitations of X-ray crystallography in studying protein dynamics, and then provide an overview of different computational methods that are instrumental in understanding the dynamics of proteins and biomacromolecular complexes.
Highlights
Ever since the first protein structure was solved sixty years ago [1], X-ray crystallography has been the most important experimental method for understanding protein structure and relating it to its function
Having described the limitations in obtaining structural and dynamic information using X-ray crystallography, we proceed to review the recent advances in experimental methods that contributed in overcoming these limitations
The realization of the importance of dynamics and the concomitant improvement in the accuracy and applicability of computational methods to be able to study the functional dynamics of proteins in native-like environments heralded the era of computation-driven structural biology
Summary
Ever since the first protein structure was solved sixty years ago [1], X-ray crystallography has been the most important experimental method for understanding protein structure and relating it to its function. Out of over 140,000 structures in the Protein Data Bank (PDB), about 90% were determined using X-ray crystallography These structures contributed to shedding light on many important biological phenomena by providing mechanistic insight into the functions of the proteins involved in biological processes [2]. Limitations of crystallography for providing insight into the conformational dynamics of biological macromolecules can be complemented by several experimental methods for studying solution dynamics. These include nuclear magnetic resonance (NMR) spectroscopy, small-angle X-ray scattering (SAXS), hydrogen exchange mass spectrometry (HX-MS), and recently, cryo-electron microscopy. We conclude the review with some of the limitations of computational methods and the future prospects
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