4 ms·

Attempting to turn this more constructive: How would you define "actual" progress? None of the results linked above are immediate disease cures, but that's nor

by an_ko 7y ago

Attempting to turn this more constructive: How would you define "actual" progress? None of the results linked above are immediate disease cures, but that's normal. Most research is an unsexy sequence of small increments of progress.

ramraj07 7y ago
During my decade long stint working in labs that worked more closer to actual therapies, I've never once referred to a mol.dyn paper or needed those results. Crystallography, sure. Super useful. Mol Dynamics or folding experiments not exactly. Which is fine for basic science, I'm sure there's a possibility some of these folding experiments will lead to insights of actual use in the long-term. However folding@home et al disingenuously portray this immediate effect on curing aids or the latest scare, which I doubt is truly that useful. I'd argue that this simulation research is as useful for covid19 therapeutic research as banning plastic straws is to solve global warming.
- l33tman 7y ago
  I know this is usually the case (having worked a few years with molecular dynamics) but would be really interesting to get your opinion on what could be done better, where the bottlenecks are (tools or knowledge or just CPU-power) etc. Would you mind sharing some thoughts here or get in touch for some chatting?
  - ramraj07 7y ago
    Disclaimer - I probably did work somewhat far from protein folding research, but still could be considered a "potential consumer" for such research since projects in my lab for example tried to make a therapeutic protein better by structural modification based on structures published by others. I will say that there's nothing wrong with continuing the folding research that's being done. We have a ways to go before purely predicted protein structures (as opposed to structures from crystallography or EM) become trustworthy enough to make research decisions based off of. But we can't get there if we don't continue the basic research! In that sense I'm all for these studies. A lab I always appreciate (purely from perceived merit of the papers I see continuously from) is that of David Baker. They seem to make meaningful strides towards making synthetic protein folding more powerful as a tool among other projects. However what I see as problems are two things in this field: 1. Definitely have seen papers where they'll try to do some molecular Dynamics simulations on some protein related to a disease but it's not clear if it's meaningful to anyone - people actually working on the disease therapy probably weren't even asking for these insights if there were even any; these low-hanging-fruit studies also don't aid the progress of folding and Dynamics research either, because they were just applying standard techniques to a problem domain. Often times these are just cash grabs by researchers who have specialized in the mol.dyn fields and end up writing grants to disease research agencies allegedly in aid of curing the disease but practically not. I know this because my lab did this blatantly. When anthrax was a real threat we got funds for anthrax related research, then we shifted to MS, now cancer. I wouldn't be surprised if they suddenly write grants for corona virus related research! This goes on in all these fields. 2. I argue that folding@home keep advertising misleadingly that they're gonna help cure aids or corona or whatever. I don't think they are, not directly. In a very vague way this feels more like war profiteering to me - these experts are exploiting the current fears to canvas their projects (even design them around this) and giving what is closer to false hope than anything that people are contributing towards end goals of curing disease. I feel like they should be honest about it - this is more basic research than anything else, so they should just say they want computational power for basic science. If people still choose to give their resources, great. Otherwise at least you live and die with dignity. Anyways this is of course a rant from a PhD who got sick of the system and left, and someone with only an associative knowledge of this particular field. Hence these thoughts should be taken with a grain of salt!
    - l33tman 7y ago
      Thanks for the insights! One thing though, protein folding is just one tiny bit of molecular dynamics research (and not really crucial at that often, due to the rise of high res cryo EM and good xray crystallography), so I would hope there are other uses for md.. I studied protein "mechanical" function/dynamics itself, and its manipulation by ligands, for example, and would hope that stuff like that would eventually seem useful to pharma companies. But yeah, the md crowd should have tighter communication with the therapeutics crowd! BTW just because you switch around your research-targets when funding changes doesn't imply that the research is useless. For example right now there is a lot of money funnelled into corona-research (for obvious reasons). I do agree it's difficult to formulate how to ask for donations (money or cpu-time), you need to seem optimistic otherwise nobody would do it but research takes a huge amount of money and cpu-time and calendar time so there surely is a gap here between expectations and reality..
      - slizard 7y ago
        > I do agree it's difficult to formulate how to ask for donations (money or cpu-time), you need to seem optimistic otherwise nobody would do it but research takes a huge amount of money and cpu-time and calendar time so there surely is a gap here between expectations and reality.. And there is a tricky balance between over-promising and under-delivering vs being realistic and lacking enough "flashyness" to get funded/thrown money at.
- slizard 7y ago
  My colleagues run numerous projects that transfer knowledge between computational research, including molecular simulations, and wetlab research as a routine. Computational and wetlab experiments are reguarly designed to complement each-other. Examples of numerous bio-phyiscs/bio-chemistry research done around me (ranging from research on ion channel dynamics [1] to drug permeability through the skin barrier [2,3], or cryo-em structure refinement just to name a few) strongly contradicts your experience as well as your final statement -- and than we've not even mentioned the drug binding affinity computations which is these days routinely done using molecular dynamics by both academia a pharma industry. [1] https://doi.org/10.1016/j.celrep.2018.03.10 https://doi.org/10.1016/j.celrep.2018.03.10 [2] https://doi.org/10.1016/j.jsb.2018.04.005 https://doi.org/10.1016/j.jsb.2018.04.005 [3] https://doi.org/10.1016/j.jconrel.2018.05.026 https://doi.org/10.1016/j.jconrel.2018.05.026
- lttlrck 7y ago
  It’s hard to tell if that’s a misinformed jab at plastic straw bans or you’re deliberately drawing attention to the misconception that the ban is due to global warming. Either way, in a time of misinformation it’s worth clarifying: “The main reason cited for eliminating plastic straws is their negative impact on our oceans and marine wildlife. Plastic in the ocean is a huge problem — look no further than trash island, or the viral video of a turtle suffering as a result of ocean pollution, to understand that. But of all the plastic that ends up in the ocean, straws make up only four percent of that waste.” https://squareup.com/us/en/townsquare/why-plastic-straws-are-being-banned https://squareup.com/us/en/townsquare/why-plastic-straws-are...
  - caycep 7y ago
    4% reduction is still 4%. I wonder if there is an opportunity to jump start the glass/ceramic industry...

by an_ko 7y ago

ramraj07 7y ago

During my decade long stint working in labs that worked more closer to actual therapies, I've never once referred to a mol.dyn paper or needed those results. Crystallography, sure. Super useful. Mol Dynamics or folding experiments not exactly. Which is fine for basic science, I'm sure there's a possibility some of these folding experiments will lead to insights of actual use in the long-term. However folding@home et al disingenuously portray this immediate effect on curing aids or the latest scare, which I doubt is truly that useful. I'd argue that this simulation research is as useful for covid19 therapeutic research as banning plastic straws is to solve global warming.

l33tman 7y ago
I know this is usually the case (having worked a few years with molecular dynamics) but would be really interesting to get your opinion on what could be done better, where the bottlenecks are (tools or knowledge or just CPU-power) etc. Would you mind sharing some thoughts here or get in touch for some chatting?
- ramraj07 7y ago
  Disclaimer - I probably did work somewhat far from protein folding research, but still could be considered a "potential consumer" for such research since projects in my lab for example tried to make a therapeutic protein better by structural modification based on structures published by others. I will say that there's nothing wrong with continuing the folding research that's being done. We have a ways to go before purely predicted protein structures (as opposed to structures from crystallography or EM) become trustworthy enough to make research decisions based off of. But we can't get there if we don't continue the basic research! In that sense I'm all for these studies. A lab I always appreciate (purely from perceived merit of the papers I see continuously from) is that of David Baker. They seem to make meaningful strides towards making synthetic protein folding more powerful as a tool among other projects. However what I see as problems are two things in this field: 1. Definitely have seen papers where they'll try to do some molecular Dynamics simulations on some protein related to a disease but it's not clear if it's meaningful to anyone - people actually working on the disease therapy probably weren't even asking for these insights if there were even any; these low-hanging-fruit studies also don't aid the progress of folding and Dynamics research either, because they were just applying standard techniques to a problem domain. Often times these are just cash grabs by researchers who have specialized in the mol.dyn fields and end up writing grants to disease research agencies allegedly in aid of curing the disease but practically not. I know this because my lab did this blatantly. When anthrax was a real threat we got funds for anthrax related research, then we shifted to MS, now cancer. I wouldn't be surprised if they suddenly write grants for corona virus related research! This goes on in all these fields. 2. I argue that folding@home keep advertising misleadingly that they're gonna help cure aids or corona or whatever. I don't think they are, not directly. In a very vague way this feels more like war profiteering to me - these experts are exploiting the current fears to canvas their projects (even design them around this) and giving what is closer to false hope than anything that people are contributing towards end goals of curing disease. I feel like they should be honest about it - this is more basic research than anything else, so they should just say they want computational power for basic science. If people still choose to give their resources, great. Otherwise at least you live and die with dignity. Anyways this is of course a rant from a PhD who got sick of the system and left, and someone with only an associative knowledge of this particular field. Hence these thoughts should be taken with a grain of salt!
  - l33tman 7y ago
    Thanks for the insights! One thing though, protein folding is just one tiny bit of molecular dynamics research (and not really crucial at that often, due to the rise of high res cryo EM and good xray crystallography), so I would hope there are other uses for md.. I studied protein "mechanical" function/dynamics itself, and its manipulation by ligands, for example, and would hope that stuff like that would eventually seem useful to pharma companies. But yeah, the md crowd should have tighter communication with the therapeutics crowd! BTW just because you switch around your research-targets when funding changes doesn't imply that the research is useless. For example right now there is a lot of money funnelled into corona-research (for obvious reasons). I do agree it's difficult to formulate how to ask for donations (money or cpu-time), you need to seem optimistic otherwise nobody would do it but research takes a huge amount of money and cpu-time and calendar time so there surely is a gap here between expectations and reality..
    - slizard 7y ago
      > I do agree it's difficult to formulate how to ask for donations (money or cpu-time), you need to seem optimistic otherwise nobody would do it but research takes a huge amount of money and cpu-time and calendar time so there surely is a gap here between expectations and reality.. And there is a tricky balance between over-promising and under-delivering vs being realistic and lacking enough "flashyness" to get funded/thrown money at.
slizard 7y ago
My colleagues run numerous projects that transfer knowledge between computational research, including molecular simulations, and wetlab research as a routine. Computational and wetlab experiments are reguarly designed to complement each-other. Examples of numerous bio-phyiscs/bio-chemistry research done around me (ranging from research on ion channel dynamics [1] to drug permeability through the skin barrier [2,3], or cryo-em structure refinement just to name a few) strongly contradicts your experience as well as your final statement -- and than we've not even mentioned the drug binding affinity computations which is these days routinely done using molecular dynamics by both academia a pharma industry. [1] https://doi.org/10.1016/j.celrep.2018.03.10 https://doi.org/10.1016/j.celrep.2018.03.10 [2] https://doi.org/10.1016/j.jsb.2018.04.005 https://doi.org/10.1016/j.jsb.2018.04.005 [3] https://doi.org/10.1016/j.jconrel.2018.05.026 https://doi.org/10.1016/j.jconrel.2018.05.026
lttlrck 7y ago
It’s hard to tell if that’s a misinformed jab at plastic straw bans or you’re deliberately drawing attention to the misconception that the ban is due to global warming. Either way, in a time of misinformation it’s worth clarifying: “The main reason cited for eliminating plastic straws is their negative impact on our oceans and marine wildlife. Plastic in the ocean is a huge problem — look no further than trash island, or the viral video of a turtle suffering as a result of ocean pollution, to understand that. But of all the plastic that ends up in the ocean, straws make up only four percent of that waste.” https://squareup.com/us/en/townsquare/why-plastic-straws-are-being-banned https://squareup.com/us/en/townsquare/why-plastic-straws-are...
- caycep 7y ago
  4% reduction is still 4%. I wonder if there is an opportunity to jump start the glass/ceramic industry...