Excellent post, thanks for putting so much work into a clear explanation. I will re-investigate Ling’s work more carefully, and also see if I can find the mistakes in his thermodynamics calculations you mention. I have been biased towards his work and not looking critically enough, because it seems to explain some surprising observations about drug activity I’ve found in my own research- but that’s no excuse.
I am interested in the possibility that Ling could be entirely wrong about membrane physiology, but this gel phase shift phenomena could still be important in the cell. If Ling and Pollack are wrong about long distance effects from protein surfaces, that might not destroy their arguments as the cytosol is very dense, and the distance between proteins is very short. Albert Szent-Györgyi also did some work on this idea that is very different from Ling’s.
One of my committee members works on physics simulations of protein hydration shells, and I am going to meet with him and see what he thinks about this. The simulations I have seen don’t show significant water structuring, as the water molecules have too much thermal energy.
I promise I’ll get my top level post made soon—I just finished my committee meeting a few hours ago.
The short and dirty version is that Ling seems to completely ignore the entropy contribution to the Gibbs free energy change associated with ATP hydrolysis and throws out about 3⁄4 of the enthalpy contribution on the grounds that it is the energy of solvation of the protons that come off the newly deprotonated middle phosphate rather than the potential energy of the phosphate-phosphate bond itself, when that simply doesn’t matter and you just can’t do that when considering equilibrium and reaction rates and the ability of one reaction coupling to another to drive it. It’s not as if that one bond alone charges up a battery or something, the whole reaction occurs.
I honestly don’t know what to make of the assertion that ATP unwinds proteins just by complexing with unwound backbone. I’ve never seen that claim anywhere else, and I use ATP all the time via standard active-site hydrolysis reactions to drive DNA-building and DNA-modifying reactions as I make the DNA I put into my modified cells.
The simulation I was speaking of about the SNARES was indicating small hydration shells just a molecule or two wide, not large ones. It was interesting though in that it found that when the two membranes were forced into odd geometries and very close proximity by the SNARES forming a tight ring, the hydration shells were forced together to form ordered structures just a few molecules wide between the membranes before suddenly emptying the space. It’s been a while since I’ve seen that paper though, and I’d encourage you to look at the folding@home website and find it if you are curious and you don’t trust my memory (which I do not entirely trust myself, that’s not exactly my field and it’s been a few years).
Odd drug metabolism stuff eh? Want to move that to a PM?
Excellent post, thanks for putting so much work into a clear explanation. I will re-investigate Ling’s work more carefully, and also see if I can find the mistakes in his thermodynamics calculations you mention. I have been biased towards his work and not looking critically enough, because it seems to explain some surprising observations about drug activity I’ve found in my own research- but that’s no excuse.
I am interested in the possibility that Ling could be entirely wrong about membrane physiology, but this gel phase shift phenomena could still be important in the cell. If Ling and Pollack are wrong about long distance effects from protein surfaces, that might not destroy their arguments as the cytosol is very dense, and the distance between proteins is very short. Albert Szent-Györgyi also did some work on this idea that is very different from Ling’s.
One of my committee members works on physics simulations of protein hydration shells, and I am going to meet with him and see what he thinks about this. The simulations I have seen don’t show significant water structuring, as the water molecules have too much thermal energy.
I promise I’ll get my top level post made soon—I just finished my committee meeting a few hours ago.
The short and dirty version is that Ling seems to completely ignore the entropy contribution to the Gibbs free energy change associated with ATP hydrolysis and throws out about 3⁄4 of the enthalpy contribution on the grounds that it is the energy of solvation of the protons that come off the newly deprotonated middle phosphate rather than the potential energy of the phosphate-phosphate bond itself, when that simply doesn’t matter and you just can’t do that when considering equilibrium and reaction rates and the ability of one reaction coupling to another to drive it. It’s not as if that one bond alone charges up a battery or something, the whole reaction occurs.
I honestly don’t know what to make of the assertion that ATP unwinds proteins just by complexing with unwound backbone. I’ve never seen that claim anywhere else, and I use ATP all the time via standard active-site hydrolysis reactions to drive DNA-building and DNA-modifying reactions as I make the DNA I put into my modified cells.
The simulation I was speaking of about the SNARES was indicating small hydration shells just a molecule or two wide, not large ones. It was interesting though in that it found that when the two membranes were forced into odd geometries and very close proximity by the SNARES forming a tight ring, the hydration shells were forced together to form ordered structures just a few molecules wide between the membranes before suddenly emptying the space. It’s been a while since I’ve seen that paper though, and I’d encourage you to look at the folding@home website and find it if you are curious and you don’t trust my memory (which I do not entirely trust myself, that’s not exactly my field and it’s been a few years).
Odd drug metabolism stuff eh? Want to move that to a PM?