advances-in-protein-chemistry

Figure 6: At Domain Level, Protein Dynamics Control Various Processes.
In cells, membrane channels and receptors are often assembled into macromolecular complexes in specialized sub-cellular domains
for the dynamic control of diverse cellular events. For instance, forming quaternary complexes of receptors, such as the EGF receptor or
the PDGF receptor is necessary for initializing cascades of signaling events for cell growth and proliferation [15].
Figure 7: Membrane Channels and Receptors are assembled into Macromolecular Form for the Dynamic Control of Diverse Cellular Events.
The function of ion transport proteins, such as the cystic fibrosis transmembrane conductance regulator (CFTR) or sodium–phosphate
co-transporter 2a (NaPiT2a), is regulated by a network of interactions with other membranous proteins like G-protein coupled receptors
and other ion channels by forming membrane oligomers either directly, or via cytosolic proteins as adapters or scaffolds. Forming large
adherence membrane complexes at the cell-cell junctions is essential to maintain tissue integrity and to suppress tumor cell invasion [16-
18]. Understanding how transmembrane protein complexes are regulated and deregulated in disease state can help to identify elements
as target to treat various diseases. Protein dynamics arises as a result of interplay between the mechanical forces and the thermal forces
(the forces due to the collision of the protein with solvent molecules). These thermal forces are random in magnitude and direction, help
protein for a process called as diffusion. A freely diffusing object displays motion, called Brownian motion, with frequent changes in
the direction and speed of its movement. Proteins obey Brownian dynamics. The world in which proteins function is characterized by
the presence of a significant amount of noise and the resultant diffusion of protein subunits arising from thermal motion. This thermal
motion is indispensable for the protein to attain its equilibrium state.
Importance of conformational flexibility
The conformational flexibility of amino acids is a major contributor in the biochemical functionality of proteins (Dodson and
Verma, 2006; Teilum et al., 2009). Protein motions are of functional significance having range from fast (sub-nanosecond) atomic level
fluctuations to slow (microsecond upward), large-scale amino acid residues conformational reorganization [19] Henzler-Wildman et
al., 2007). It has been observed by several studies internal motions of protein is directly related to biochemical functions [20] Smock
and Gierasch, 2009) and normal mode analysis helps in the identification of categorization and prediction of large-scale conformational
changes in the protein (Ma, 2005) and elastic-network models (Hall et al., 2007; Keskin et al., 2000) has been quite successful too.
Molecular Dynamics (MD) simulations are effectively helpful to investigate the conformational energy landscape (Karplus and Kuriyan,
2005; Karplus and McCammon, 2002) and approaching the idea that how protein dynamics relates back to sequence.
Proteins: Flexible nanoparticles
Proteins are flexible nanoparticles that commonly achieve their biological function by collective atomic motions. Flexibility refers
that protein molecules are able to change their conformation in the biological system more quickly than any other macromolecule
especially in membranous system. Such motions may be differentiated by hinge, shear, or rotational motions of entire protein domains,
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