tag:blogger.com,1999:blog-9633767.post7333697403336195514..comments2024-03-18T06:11:04.848-07:00Comments on The Curious Wavefunction: The fundamental philosophical dilemma of chemistryWavefunctionhttp://www.blogger.com/profile/14993805391653267639noreply@blogger.comBlogger12125tag:blogger.com,1999:blog-9633767.post-2802548535538719302016-06-20T18:34:51.162-07:002016-06-20T18:34:51.162-07:00Could one, theoretically, come up with a program t...Could one, theoretically, come up with a program that takes all interactions (and all known information) into consideration and run the experiment through that on a "smaller" scale? I have seen some that do this for physics labs. Is it possible with Chemistry? I think that making a program like this would be a really cool project. It would be a lot of work to input all the data but the outcome would be a pretty awesome virtual chem lab. You could change scale and slow down or speed up reactions. Chem is not my strong suit, so excuse me if this is an ignorant question. Audreyhttps://www.blogger.com/profile/13484985417928533371noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-60397967078583790132015-11-01T18:00:50.976-08:002015-11-01T18:00:50.976-08:00Excellent article, but things are clearly not that...Excellent article, but things are clearly not that hopeless. We can use these concepts to predict reactivity and reaction mechanisms, and do complicated organic syntheses. When considering drug protein interactions, it is impossible to systematically vary every amino acid in the protein -- there aren't enough atoms in the universe. Even doing this for 10 or so surrounding the target for a ligand involves 20^10 power. We are just beginning to find out how subtle and far reaching allosteric effects can be. A fascinating study of everything changing, when one very small ligand moves in a fairly simple protein is -- [ Science vol. 350 pp. 381, 445 - 450 '15 ] when CO is photo-dissociates from heme -- everything starts moving in under 1 picosecond.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-9633767.post-23681257963037663332015-10-01T02:45:21.388-07:002015-10-01T02:45:21.388-07:00Hi I enjoyed and (amazingly!) understood this post...Hi I enjoyed and (amazingly!) understood this post. There is a lucid beauty in looking at things as they are and appreciating the knowns and the unknowns. Posts like this can make daunting science less so. Congrats on the prize.ShankarMonyhttps://www.blogger.com/profile/03675954431716900086noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-18094281170679281492015-09-29T20:45:21.093-07:002015-09-29T20:45:21.093-07:00I am going to paraphrase this a bit and you tell m...I am going to paraphrase this a bit and you tell me if I am completely off. <br /><br />The issue is that you are dealing with a multi-particle system and that you cannot remove a piece of the puzzle and expect the landscape to change just locally. The impact of any changes is to change the global landscape and so it is very hard to build an overall change in the global landscape through minute changes in each local phase space changes. <br /><br />Kind of like how in GR you can build a full picture of a physical interaction by integrating over many many different inertial frames each of which is sort of a small change in the grand scheme of things, but adds up to the global one (however complicated and horrific this integral might be, there is at least in theory a path). However no such thing exists in Chemistry?Pinkesh Patelhttp://www.facebook.com/pinkeshnoreply@blogger.comtag:blogger.com,1999:blog-9633767.post-57302816720327181192015-09-08T11:12:00.339-07:002015-09-08T11:12:00.339-07:00That's a good point. The lack of controlled ex...That's a good point. The lack of controlled experiments is a problem with biology too.Wavefunctionhttps://www.blogger.com/profile/14993805391653267639noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-59877298425454719042015-07-28T19:52:46.964-07:002015-07-28T19:52:46.964-07:00Ash, I think you might be needlessly giving chemi...Ash, I think you might be needlessly giving chemistry as a field the short stick with this one. In molecular and cellular biology we consider quality knock-outs to be single variable changes, but in reality they are not even in absence of off-target effects. We pretend they change one variable (the target of interest) but in reality we know they change the system. I suppose those fall into the chemical systems you cover in the last paragraph.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-9633767.post-6494392402382999502015-07-01T07:52:37.025-07:002015-07-01T07:52:37.025-07:00Thanks for commenting, and great to know that you ...Thanks for commenting, and great to know that you were one of the original 'pioneers' at Schrodinger! I bet you know the travails of doing something like this as well as anyone...Wavefunctionhttps://www.blogger.com/profile/14993805391653267639noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-72268954408697604872015-06-30T23:35:15.898-07:002015-06-30T23:35:15.898-07:00Thanks for writing this so clearly and entertainin...Thanks for writing this so clearly and entertainingly. I'm a math teacher now (and saw a link to this from @MrHonner on Twitter, another math teacher), but worked for schrodinger.com in the 1990s (I was employee #5, I see they're now at 300+), so I chuckled at "I suppose you could do it computationally... but as we all know that comes with its own litany of problems." Yes, as the grant writer/customer support person, I remember trying to talk our way through some of those. Julie Wrighthttp://twitter.com/@msjwright2noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-2958967469992216422015-06-30T06:46:02.849-07:002015-06-30T06:46:02.849-07:00Good point Pete: You can't truly turn off an i...Good point Pete: You can't truly turn off an interaction and keep the effect local. I suppose you could do it computationally to some extent (and people do do things like turning off electrostatics or vdW interactions) but as we all know that comes with its own litany of problems...Wavefunctionhttps://www.blogger.com/profile/14993805391653267639noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-37295949206127428732015-06-30T04:15:52.339-07:002015-06-30T04:15:52.339-07:00Hi Ash, There is also a more subtle issue here and...Hi Ash, There is also a more subtle issue here and I’ll use your example of trying to assess the contribution of a hydrogen bond. Suppose we could magically switch the hydrogen bonding off by turning the amide into something that looked like hydrocarbon? The problem is that the ‘hydrocarbonized’ amide still interacts with the environments in which it exists. We can use matched molecular pair analysis to show that one hydrogen bond contributes more (relative to a given reference state) than does another hydrogen bond acceptor. However, we can’t assign absolute contributions to the two hydrogen bonds.<br /><br />As you’ve correctly noted, the contribution of an intermolecular contact to affinity is not an experimental observable. Molecular recognition in aqueous media is controlled by non-local interactions. Some components of binding free energy (e.g. entropy changes, conformational energy penalties) are fundamentally non-local and it would not be possible to assign them to specific intermolecular contacts even in gas phase. <br />Peter Kennyhttps://www.blogger.com/profile/12180360326821860667noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-12961482932089987052015-06-29T19:08:27.833-07:002015-06-29T19:08:27.833-07:00That's a great way to put it!That's a great way to put it!Wavefunctionhttps://www.blogger.com/profile/14993805391653267639noreply@blogger.comtag:blogger.com,1999:blog-9633767.post-73357135921771776532015-06-29T17:51:38.567-07:002015-06-29T17:51:38.567-07:00"bonds mean short distances,but short distanc..."bonds mean short distances,but short distances don't mean bonds" This reminded me of Cotton's words on metal-metal bonding. Let me quote from the book Multiple Bonds Between Metal Atoms:<br /><br /> “Bond lengths are facts; bond orders are not. In the process of inferring a bond order from a bond length one is often getting out no more than what was put to begin with. …Experience is the only test, and experience thus far has shown that M-M bonds cannot usefully be treated in such a way. ..We condemn as foolish and hopeless any effort to associate a unique, precise, quantitative bond order with each and every M-M internuclear distance.”<br /><br />F. A. Cotton, C. A. Murillo and R. A. Walton, Multiple Bonds Between Metal Atoms, Springer Science and Business Media. Inc., New York, 2005, pp 707Chemdiaryhttps://www.blogger.com/profile/06428076032546974013noreply@blogger.com