Now that we’ve talked in general terms about how molecules and bend and twist and interact I feel that it’s important to cover the idea of why. Why do molecules move around in the way that they do? It turns out that the natural world, just like us, can be very lazy sometimes. Nearly everything wants to get its job done while using the minimal amount of energy possible. In a more scientific term we say that it a system (which can be anything from an entire animal to a single molecule) always wants to “minimize it’s free energy”. In our example with biotin and streptavidin, biotin packs its way inside of streptavidin because it uses “less” free energy if it is inside the streptavidin pocket versus in water. An important way to represent free energy is with Gibbs free energy, represented as: dG or ΔG. There are two main components of free energy: enthalpy (ΔH) and entropy (ΔS) and are represented in Gibbs’ equation:
ΔG = ΔH – TΔS
I want to talk about them very briefly in this post in the context of my previous work with peptides. Hopefully this will provide a framework for understanding the more complicated hypothetical stuff that I want to work in in the future.
The first component of Gibbs equation is Enthalpy (ΔH). Enthalpy is an important function in the field of Thermodynamics, we can think of it as the amount of energy a system can absorb as heat. We know from our everyday lives that, in general, heating something up breaks it down. You can think of melting a chunk of metal or putting cubes of sugar into a coffee. In the peptide world, the movement of heat (or changes in enthalpy), are obtained by breaking and forming bonds like hydrogen bonds. If putting heat into a bond breaks it then, in general, reforming that broken bond must send the heat out again. Hydrogen bonding is very important for protein and, in particular, membrane active peptides (MAPs). A significant portion of my understanding of MAPs comes from working with Dr. William Wimley at Tulane University. Dr. Wimley’s work with Steve White showed that peptides that are able to hydrogen bond require less free energy to squeeze into a lipid membrane, similar to Biotin squeezing into streptavidin. Changes in enthalpy can dictate how and when molecules form bonds and how those bonds can be broken as well.
Enthalpy is often opposed or balanced out by changes in the Entropy (ΔS) of a system. Entropy is a very abstract idea that gains different interpretations from different fields. Let’s talk about Entropy, for the sake of our Molecular Yoga analogy, as the number of poses a single molecule can take. If a set of molecules can take three poses: >, ^, and < versus, say, two poses >, ^, and ^ then it is said to have greater Entropy. Molecules like to be able to assume as many poses as they possibly can. Why would they want to bend and twist in different ways? Lets think about MAPs again. Peptides that can move around and form different shapes have greater ability to survive different conditions. For example, they can better wiggle to get themselves into a membrane. This thought reminds me also of the paper we discussed a few weeks ago. A peptide with greater degrees of freedom (i.e. entropy) could be better able to hide RNA that could reproduce it and hence could be more evolutionarily favorable. The entropy of a system tends to oppose the enthalpy. Giving up heat leads to bond formation but therefore there are less open bonds to rotate and move about. Through the balancing of these two components of Free Energy we can try to predict the motion of molecules.
Entropy and Enthalpy are important concepts for understanding thermodynamics and molecular motion. I hope I’ve provided a little bit of insight into what they are so I can discuss more theoretical concepts. If you want to learn more you can turn to some of the resources I used in grad school:
Gaskell’s book: Introduction to the Thermodynamics of Materials ISBN 9781591690436
And also Georgia State University’s website Hyper Physics gives some pretty good interactive examples as well: http://hyperphysics.phy-astr.gsu.edu/hbase/hframe.html
Or feel free to stop by and chat with me! Thanks for reading!