Conformational dynamics induced by mechanical or biochemical constraints in biological systems, such as DNA and proteins, is a central issue for biologists and remains challenging for physicists. Indeed, it is of paramount importance in understanding biomolecular interactions and directly concerns the understanding of equilibrium and out-of-equilibrium processes in vivo. The idea is that a global overview of the systems' energy surface is useful for a quantitative understanding of the relationships between structure, dynamics, stability, and biological functions. Thanks to the continuous increase of the computing power and of the reliability of empirical force fiels, molecular dynamics (MD) simulations have become a widely employed computational technique to simulate the complex dynamics of these complex biological systems.
Both protein and nucleic acids are flexible entities, and dynamics can play a key role in their functionality. Proteins undergo significant conformational changes while performing their function. As a rule, any complex made by any protein implies some structural rearrangement. Larger conformational changes are also present in the known protein structures. For instance, loop or domain closures contribute to isolate the active site from the solvent molecules and, in so doing, alter the chemical environment . Also, allostery is the most common regulation strategy. Allosteric regulation is entirely based on the possibility of a given protein to coexist in two or more conformations of comparable stability. Binding to ligands (allosteric regulators), or simply protein concentration, or crowding, may switch stabilities among conformations and trigger the shape transition. Additionally, some features of protein function can be understood only when dynamic properties are taken into account. For instance, diffusion of small substrates through heme-dependent enzyme molecules requires the transient appearance of channels in the protein structure. Also, cavities have transient phenomena that in some cases can only be revealed or analyzed following its dynamics. In the case of nucleic acids, conformational changes are even more complex. Standard B-DNA has a relatively simple structure in comparison with protein or complex RNAs; however, it is an extremely plastic molecule that undergoes large conformational changes to adapt to its interaction partners. Binding of transcription factors to DNA, for example, is not only dependent on DNA sequence recognition, but also a direct consequence of the ability of the DNA molecule to adapt to the protein surface.
F. Sicard and A.O. Yazaydin*, Biohybrid membrane formation by directed insertion of Aquaporin into a solid-state nanopore, submitted for publication (2022)
M. Faulkner, I. Szabó, S.L. Weetman, F. Sicard, R.G. Huber, P.J. Bond, E. Rosta*, L-N. Liu*, Molecular simulations unravel the molecular principles that mediate selective permeability of carboxysome shell protein, Sci. Rep. 10, 17501 (2020)
F. Sicard*, N. Destainville, P. Rousseau, C. Tardin, and M. Manghi, Dynamical control of denaturation bubble nucleation in supercoiled DNA minicircles, Phys. Rev. E 101 (1), 012403 (2020)
F. Sicard*, N. Destainville, and M. Manghi, DNA denaturation bubble: free-energy landscape and nucleation/closure rates, J. Chem. Phys. 142, 034903 (2015)
F. Sicard* and P. Senet, Reconstructing the free energy landscape of Met-enkephalin using dihedral principal component analysis and metadynamics, J. Chem. Phys. 138, 235101 (2013)
* Corresponding author
last update: July 2020