Physics behind structural biology-An interdisciplinary research field

The novel coronavirus, SARS-CoV-2, has stretched to pandemic status. Scientists are tirelessly doing work to understand the virus activity and develop vaccines. The functionality, viral dynamics is still a mystery. Perhaps structural as well as macromolecule play an important role for understanding the viral activity. Function of biological macromolecules is possible to be explored through structural biology study. As the basis of drug design, structural biology helps determining viral structure since early 1990s. Hence physics comes forefront to device modern techniques such as automation and cryo-electron microscopy (cryo-EM).

Physics-based practices find enormous role in the field of structural biology. Mostly the structure of biological macromolecule is determined by X-ray crystallography, which starts in 1934, when John Desmond Bernal and Dorothy Hodgkin found the first X-ray pattern of a crystallized digestive enzyme pepsin. Later on, Dr. Hodgkin successfully applied X-ray crystallography to determine the structure of penicillin in 1946 and also obtained the structure of vitamin B12 in 1956 with the physics modality. One must tag the X-ray crystallographic determination as physics modality because it starts from the work of physicists such as Wilhelm Röntgen, who invented X-rays; Max von Laue, who revealed that X-ray wavelengths are in the range of inter-atomic distances and William Lawrence Bragg, who exhibited the utility of diffraction pattern for analysing the crystal structure. Dorothy Hodgkin put the X-ray crystallography in a very practical form for the determination of biological macromolecule, due to which, Hodgkin credited winner of the 1964 Nobel Prize for Chemistry

Besides, other modalities as application of physics driven working principle play important role in structural biology. They include NMR/I, electron microscopy, confocal microscopy, computation etc. In conjunction with molecular engineering these modalities are very efficient to explore macromolecular structures, energetics, and dynamics. Experimental strategies are supplemented by computational and theoretical approaches.

Nowadays, sequence and protein data are available. Biophysics are going to be a prime research field to apply different physical laws on the sequence data. Many theoretical approaches for analyzing protein structures, biomolecules are now an important tool to explore the structural biology. In this crisis period of COVID-19, physical theory is very helpful to understand the disease dynamics. It includes protein aggregation in cells, conformational dynamics of enzymes, cell penetration by viruses, DNA recognition by proteins, and protein folding. The experimental data are not sufficient to understand the virus infection, unless a solid background based on physical laws are taken much care of. Therefore, it is very important to establish interdisciplinary research field- Physics behind Structural Biology.

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