tag:blogger.com,1999:blog-9633767.post4480105807432414214..comments2024-03-25T09:11:17.877-07:00Comments on The Curious Wavefunction: In which creationists' understanding of amyloid appears...tangledWavefunctionhttp://www.blogger.com/profile/14993805391653267639noreply@blogger.comBlogger4125tag:blogger.com,1999:blog-9633767.post-69607301773962942952011-09-14T12:31:40.798-07:002011-09-14T12:31:40.798-07:00True!True!Wavefunctionhttps://www.blogger.com/profile/14993805391653267639noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-85823390491971961882011-09-14T10:38:54.231-07:002011-09-14T10:38:54.231-07:00“In fact one can even make an argument that a ther...“In fact one can even make an argument that a thermodynamically superstable state might lead to an evolutionary dead end since it will be hard to tinker with.”<br /><br />That impression is surely correct, but I would suggest a stronger “*impossible* to tinker with,” and a dead end for sure. Indeed the most thermodynamically satisfied state of protein + water is the exhaustive hydrolysis product -- many amino acids -- by tens if not hundreds of kcal/mol. Dobson’s notions of kinetic safeguards work in both directions.DRnoreply@blogger.comtag:blogger.com,1999:blog-9633767.post-6577258056218990152011-09-13T19:07:22.257-07:002011-09-13T19:07:22.257-07:00That's a really important point. During my pos...That's a really important point. During my postdoc I played around with the protein structure prediction program Rosetta. Rosetta generates several plausible folded structures for a given sequence and assigns scores to them. Many of these structures are of course false positives (and this scoring problem is what mainly hobbles the prediction) but I wonder if the inclusion of at least an implicit cellular environment in the protocol can be possible at all. I know that there have been some efforts recently to model crowding in MD simulations; I will have to dig up references but I think a lot of work has been done by the Zhou lab at FSU physics.Wavefunctionhttps://www.blogger.com/profile/14993805391653267639noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-51229509882830962622011-09-13T18:17:24.524-07:002011-09-13T18:17:24.524-07:00Of course, the thing to keep in mind is that the e...Of course, the thing to keep in mind is that the entire possible state space is not actually what one might think it is, after all.<br /><br />The standard presentation of Levinthal’s paradox is that the unfolded polypeptide (no secondary structure or higher) is some sort of flexible long-chain heteropolymer that is free to sample the entirety of phi/psi space. That sort of picture is applicable to long-chain polymers….that are sufficiently dilute (so as to avoid intermolecular forces being important) and in a so-called “good” solvent (that is, one which maximizes attractive forces between the polymer segments and solvent molecules, and minimizes interactions between polymer segments). As we all know, a cell is hardly a dilute sort of existence for macromolecules and water – while a very suitable solvent for many compounds – does very little for the non-negligible number of hydrophobic side chains in proteins. And we all know that amino acids can and do interact with one another. I suppose this is why I have never been too worried by Levinthal’s long-ago thought experiment.<br /><br />Now, you’ve got me thinking about comparative studies of thermophilic proteins, which I know have been done to some extent, but can’t recall all the details. I have to wonder if they’re more thermodynamically stable on the average, or if it’s just a matter of shifting things proportional to their preferred growth conditions. Something to look into one of these days!<br /><br />And deliberate obfuscation from creationists? Surely you jest! ;) <br /><br />o O (Deleted the original so as to clean up my atrocious grammar.)MJhttps://www.blogger.com/profile/02796378432680640144noreply@blogger.com