Molecular dynamics simulations, gramicidin

A good understanding of the properties of water is thus essential as we move to more complicated systems. We have been involving in the study of aqueous solution of many important biological molecules, such as acetylcholine, Gramicidin, deoxydinucleoside phosphate and proflavin, and DNA, etc., first at the Monte Carlo level and slowly moving to the molecular dynamics simulations. We will discuss some of the new results on the hydration structure and the dynamics of B- and Z-DNA in the presence of counterions in the following. 

Fig. 8 Proposed model for gramicidin S in a membrane according to the orientational constraints obtained from and N-NMR. The upright backbone alignment (r 80°) and slant of the /3-sheets (p -45°) are compatible with the formation of an oligomeric /3-barrel that is stabilized by hydrogen bonds (dotted lines). A The oligomer is depicted sideways from within the lipid bilayer interior (showing only backbone atoms for clarity, but with hydrophobic side chains added to one of the monomers). Atomic coordinates of GS were taken from a monomeric structure [4], and the two DMPC lipid molecules are drawn to scale (from a molecular dynamics simulation coordinate file). The bilayer cross-section is coloured yellow in its hydrophobic core, red in the amphiphilic regions, and light blue near the aqueous surface. B Illustrates a top view of the putative pore, although the number of monomers remains speculative...

B. Roux and M. Karplus, Annu. Rev. Biomol. Struct. Dyn., 23, 731 (1994). Molecular Dynamics Simulations of the Gramicidin Channel. 

Liu, Z., Xu, Y, Tang, P. (2005). Molecular dynamics simulations of C2F6 effects on gramicidin A Implications of the mechanisms of general anesthesia. Biophysical Journal, 55(6), 3784—3791. 

In a subsequent work72 they studied the, 5N chemical shifts for a biologically relevant system, the gramicidin channel. In particular they also explored how these change when the conformation of the system is changing, whereby they used molecular-dynamics simulation to follow the structural changes. Due to... 

The structure of gramicidin A in a lipid bilayer environment has been determined using molecular dynamics simulations and solid state NMR. The obtained results underscore the utility of molecular dynamics simulations in the analysis and interpretation of structural information from solid state NMR. 

Figure 24.3 The simulation is based on the coordinates of H. Heller, M. Schaefer, and K. Schulten, Molecular Dynamics Simulation of a Bilayer of 200 Lipids inm the Gel and in the Liquid-Crystal Phases, Journal of Physical Chemistry, 97, 8343-8360 (1993) and taken from an interactive animated tutorial by E. Martz and A. Herraez, Lipid Bilayers and the Gramicidin Channel (http //molvis. sds.edu/bilayers/index.htm (2001) by courtesy of Professor Martz.

Huang P, Loew GH (1995) Interaction of an amphiphilic peptide with a phospholipid bilayer surface by molecular dynamics simulation study. J Biomol Struct Dyn 12(5) 937-956 Bemeche S, Nina M, Roux B (1998) Molecular dynamics simulations of melittin in a dimy-ristoylphosphatidylcholine bilayer membrane. Biophys J 75(4) 1603 1618 Woolf TB, Roux B (1994) Molecular dynamics simulation of the gramicidin channel in a phospholipid bilayer. PNAS 91(24) 11631 11635... 

B. Roux and M. Karplus. Molecular dynamics simulations of the gramicidin channel. Ann. Rev. Biophys. Biomolec. Struct., 23 (1994)731-761. 

Figure 2 A snapshot of a molecular dynamics simulation of a solvated lipid bilaycr with gramicidin A included. (Figure 1 in Ref. 19, reproduced by permission of the National Academy of Sciences)...

Benoit Roux s group is using molecular dynamics (MD) simulations to elucidate the fundamental principles governing the transport of ions with a special interest in constructing detailed atomic models of the gramicidin channel.29 They also use MD simulations and free energy methodologies to study... 

MD simulations of ionophore/channel molecules intercalated into a lipid bilayer would require a large number of lipid molecules to ensure that the ionophore/channel molecule does not interact with its periodic images. Still, comparisons between boundary and bulk lipids may have to be done from independent simulations to get an accurate view of how these molecules affea bilayer dynamics. Typical channels like gramicidin show ion transport times of —10 s, which is a time scale that is presently unattainable in typical MD simulations. However, one can obtain insights into the molecular aspects of the energy barriers involved in the translocation of small molecules and ions from PMF calculations, particularly when there is no ambiguity about the path of the solute movement. Moreover, short time scale (10 s) simulations can... 

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