Mr_Useless

so current technology can "see" structure from a static frozen state only but isn't there a massive gap in understanding as to why it takes so long for a protein crystal to properly form then xray crystallography to determine the structure? may be crystallography will be replaced by NMR as it develops?..It seems current technology can only look at things in isolation , one thing at a time., maybe one day NMR of a whole cell could give us lots of vital information. is the "dream" then to devise technology than can "scan" the cell in its native environment and not resort to "freezing", ? just a thought (a wild and ignorant one) why not develop ultrasound technology ? i mean if it can give us a picture of living organs why not scale it further down to detect smaller and smaller things? like a submarine can track things using sonar from such a far of distance why not the same techniques applied to cell biology? i dont know perhaps different types of proteins have some kind of unique "signature" under the sonar scan.which could figure out there structure and also track with what other proteins they interact with..!?

Doesn't that really sum up the great failure of Bioinformatics, that its perhaps the "stamp collecting" compared to the real science of biophysics? im getting way out of my depth here, but shouldn't time and money be spent on improving the imaging techniques in biophysics, to see the "actualities" of just what is going on , rather than simulations? i mean even if these calculations could be done very fast wouldn't we still have a half baked idea of whats really going on inside the cell like shouldn't "visualization" be the first port of call to improve and refine the simulation side? like a fantasy machine that could zoom in to the cell and take snap shots of a protein folding in the cell and recording with what other things it interacts , (like think of a satellite, like the earth being the cell, and the satellite can zoom in at any portion and see things in great detail) personally the idea of building such machines to actually see or figure out rather than effort spent in "predicting" sounds a lot more exciting.

thanks for the very informative internet links, @protein folding and its interactions in a solution can seem like a... Rubik's cube in some ways. The hands are the solution. The protein is the rubik's cube. that was a very interesting analogy, like the protein folding problem is one of those combinatorial explosion problems which need more more time to solve than the age of the universe! but like a person doing the rubiks cube has to keep trying and trying, one combination after another ... but with the protein like theres no "trial or error" kind of thing involved, it does it super fast every time, .. ..like the goal of the rubiks cube is the same colored sides but is it 100% certain that the goal of the protein is to form a structure with the minimum energy? or could the sequence that encodes the protein fold up to in to some kind of equilibrium which may or may not be the lowest energy? @often also require additional factors besides the solution (e.g. chaperones or co-factors). are the chaperones like really vital for folding or do they become vital only due to the crowded environment of the cell?(like bouncers at a night club, not really needed for the club to operate but necessary when crowds get out of control?!) wasn't there things like test tube folding experiments which showed you only need water and the denatured protein?

just curious: can proteins fold up properly in any other liquid other than water? @though. I have to add that designing novel artificial proteins are (to my knowledge) only met with moderate succes the very thought of designing new proteins from scratch blows my mind, do you like pick and choose what amino acids you want and then wait to see what happens? but the novel protein like keeps falling apart..was just thinking may be theres some kind of "rule of thumb" involved in selecting the amino acids in your sequence, like not to many hydrophobics ones or hydrophillic so theres some kind of balance in involved?

@or even have a role in therapy for disease. it certainly sounds exciting to see how something newly designed could affect things, perhaps some kind of "silver bullet" may be found, but isn't that like trying to fix something without knowing what the components involved are or what they look like? are diseases like cancer still waiting to be solved because we dont know the shape of the proteins and dont know how they interact? @This areas of research is under funded and staffed, but has the potential for the most futuristic gains, using one variable to tweak all the variables. that was a fascinating and inspiring, like water is the "architect" of it all, the water molecules interacting and guiding everything to correct structure..and linkage...so DNA, proteins and protein interactions are due to the interaction with water essentially.. i was just curious as to why this important field of investigation was so underfunded and under staffed? what is like the latest "fad" that is getting the staff and funding?!

thanks again for your enlightening posts, @ you can then go back to computer models for example design of proteins with new function. sorry to sound foolish but was just curious as to why there was a focus on new protein design and function when so little is known of like the ones already in nature? @One could find out that e.g. certain amino acids are the major elements of the binding pocket, however modeling could predict that the backbone structure also adds to that. Then you could change the amino acid sequence of the protein and repeat the experiments and compare it with theoretical values. Ideally you could then prove which amino acids have strong interactions with the ligand that was very interesting, is that like finding the "certainties " in protein sequences, like what stays the same, ,(apologies again for my ignorance) but how we be certain that those amino acids will interact with the ligand in the same way under any amino acid sequence that could be found in existing proteins? i mean like the "exact" amino acid sequence producing the "exact" same protein which interacts with the ligand in the "exact" same way.. but with any different combination (with those test amino acids included) might not give similar results all the time ? (sorry to sound stupid!) but would you not have to repeat your experiment with every known protein sequence (with have those test amino acids) to prove that strong interactions with the ligand was always true?

thanks again for your highly informative reply s, @So it's all the same really. Why should there be boundaries? I wouldn't want to restrict myself to one area, when they can all work together. i agree with you totally,..a holistic kind of approach , in ignorance i was just curious at like say the time and expense spent trying to predict protein structure and details using supercomputers and other fancy "algorithms" could have been better spent on like developing the sure fire techniques like NMR etc @biophysicists are mostly concerned about highly defined, small interactions thanks for shedding light, i was confusing biophysics to be totally to do with microscopy,,, so its about finding the rules through experiment and then forming the more accurate mathematical model , like the goal ultimately being the mathematical description @situations that are not easily described mathematically. could this be where the imaging microscopy technology comes in the future , so like we can kind of see what links with what @A major challenge is often to translate that information into biological function (which was my role in those projects). i hope you had success! you mentioned that you were focusing on the small concentrated details (please forgive my ignorance) but can true function be ever found from such detailed specifics? like the elephant in the room kind of thing?!

Thanks for your very informative posts, they sure did bring home the vastness of the subject and its different areas like working with the very small to scaling upwards @Some biophysicists are also working with more complex biological interactions is that like the proteins interacting with each other? @You can't really separate the two. but doesn't the "spirit" of biophysics really lie in experimental side of things though? like the modeling side going in to systems biology / bioinformatics /mathematics area? @ there is an increase in complexity of interactions from biophysicists, biochemists to biologists in my ignorance can i say that a biophysicist is a person who makes the "special microscopes" and thinks up novel experimental techniques to help the biochemist look inside the cell and its molecular parts. like knowing what the jigsaw pieces look like (structure) and how they link up and with what?

hi Ive been fascinated by this subject but find its wide variety of aspects make it difficult to understand just what Biophysics is about, am i right in thinking its split up in to two parts like theoretical and experimental ? is the theoretical part where all the mathematical modeling and computer simulation goes on ? like making predictions on how biological matter will behave and the experimental side where people focus on developing methods to "look inside" biological matter..how it all interacts , how its actually structured. i find the more experimental side appealing, but is that part of biophysics? or does that come under crystallography or microscopy ? or they part of biophysics to? Thanks