It’s been just about a year since I started this blog. Thank you to those of you who have kept interest and are reading it. I thought for today I’d try to go back to the root of what I’m interested in, talking about molecular flexibility or “molecular yoga”. I was reminded of one of the original parts of “Molecular Yoga” when reviewing a thesis presentation this past week: G. N. Ramachandran’s work on his “Ramachandran plots” from the 1960’s. Ramachandran was a famous biophysicist who was interested in the structure of proteins, specifically how they are able to bend and twist to form interesting structures. When we think of small molecules we sometimes have the tendency to assume to assume they are just small rigid shapes. In reality, many molecules have the ability to undergo some “Molecular Yoga”.
Proteins are able to from shapes other than just being a linear, tangled mess. I hope, in reading some of what I’ve wrote, you have gained insight into the fact that thermodynamic forces such as Entropy can drive molecules to wiggle about a little bit. This is exemplified in proteins, as Ramachandran showed. Take, for instance, a simple peptide formed from two amino acids bound together. The carbon atoms that are held together by single bonds are able to rotate with respect to each other.
This can allow them to move about and position, for instance, the R (random) groups in different places. Ramachandran and colleagues looked at the rotations about those angles (Phi and Psi) for the natural occurring amino acids and whether or not they cause the atoms to crash into each other. There are clustering regions on a Ramachandran plot where these angles are not causing crashing or to use a phrase we discussed earlier, are “Energetically Favorable”. Interestingly, these are the angles in which secondary structures such as alpha helices and beta sheets can be found. Thus, Ramachandran was able to provide a way for linking the favorability of bond angles to the secondary structures that occur in nature.
Figure From Griffiths et al 2002
Ramachandran plots, though they may appear simplistic, provided scientists with the basis for developing much more complex ways of looking at molecular structures. There are numerous groups working on computational modeling of proteins, and they use this type of information for their work. I, personally, am interested in how these structures can be induced to change by target binding and by other phenomena. You can see how it what my line of thinking is here as well. For proteins you need to be able to add some energy into the system to make an angle rotate from its most favorable conformation to another conformation. In my opinion, Molecular Yoga is about finding was to make this happen dynamically, not just for proteins but for many other types of molecules as well.
Thanks for reading this time. I’ll be updating on my work soon!
Ramachandran, GN, Ramakrishana, C, Sasisekharan, V. J. Mol. Biol. (1963) 7,95-99