veritas2 Lv 1
Hi everyone, here are some ideas I have.
1) Incorporate functional simulations on top of the structure simulations. For example, it would be interesting to try to simulate the effects of trypsin on an amide bond, with a way to measure the efficiency (like turnover rate)
2) De novo prediction of alpha helices, beta sheets, using ramachandran plots. I think this would be valuable, because not all helices are right handed, and beta sheets alter from parallel to anti-parallel.
3) Redefining Compactness . Definition of "compactness", from what I understand, is the tightness of a protein, thereby any holes would have a bad score. However, most proteins with a function actually remain "unfolded", and thus the accurate native state of a protein would obtain a lower score than the more accurate counter parts.
4) Incorporation of environmental factors , eg Temperature, Lighting (for the rhodopsins and, pH, counter-ions (Chlorine, etc), to simulate a more accurate folding process.
5) Like everyone else has mentioned, de novo structure design (which would require 2), which is essential to the future of de novo functional design. However, for the newly designed to be useful and incorporated into bacteria, it must be possible for the primary AA to fold into the tertiary/quaternery structures. That is to say, having a nice 3D compact protein, doesn't mean that it's AA structure will allow it to fold into such a compact fit, within reasonable accuracy, time. Not to mention that many chaperon proteins might also be needed.
6) Allow simulation of effects of post-translational modifications (PTMs). Very few proteins consist only of native amino acids, MOST actual undergo substantial PTMs, eg. phosphorylation, acetylation, ubiquitylation, sumolyation, glycosylation
On a side note, and a minor detail, the x-ray crystal structures obtained usually are missing 3 terminal amino acids due to resolution problems, are you incorporating them in your simulations?
My 6.5 cents
