Dear all!
How do You think, is it possible to run an MD simulation of the protein with a fully rotatable bond (changing amide rigidity) in the middle of the reconstructed disordered region?
I have a multi-domain protein lacking three disordered regions in each domain. For example, X-ray captured the entire domain folding, but some part (~40 residues, forming loops or something separated and flexible) is absent. There is no templates for homology reconstruction, the number of possible conformations is also enormous. Despite the evidence, that my suggestion is unreal (because of some shaperons, post-translational changes), what if I could create a randomly folded loop/region and then start an MD with some point (tricky topology parameters of the bond), dividing the loop in two segments? This 'weak' bond should allow a free rotation of two ends/segments of the loop, bounded to the domain by other ends. In this way I want to preserve the length of the loop (this modified bond in the middle of the loop will permit additional rotation, but will prohibit an increase in distance between neighboring residues, forming this bond). I thought about 'partial' REMD technique, but the domain and the loop are forming a whole strict contour due to the psi/phi geometries...
P.S. Simple MD didn't help me - the loop took some conformation, which stood stable across the MD. Maybe this is Ok. However, then why wasn't it reflected with the crystal structure?
Thank You!
Hi,
MOE and MODELLER have "loop modeler" functions that build your missing loops. They can be a good start for further MD studies. For restraining distance, you just have to spatially constrain the alpha carbons in each end.
Dear Ricardo, thank You for the respond. Well, I've already prepared the loop with MOE, as I don't like modeller with it correct spatial orientation of the template proteins... What should the alpha carbons constraining give me? On the contrary, I would like to relax eve strong bonds allowing an excessive twist/untwist of the loop contour (like negative superspiralization of DNA by topoisomerase).
The constrain of the alpha carbons of initial and terminal residues allows you to keep the distance fixed between both ends, while the rest of the loop is free to relax.
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