If conformational changes are occurring in protein structure then how will it effect Gibbs free energy of that particular protein?
The conformational changes of protein are generally coupled with processes that produce free enthalpy (such as ATP hydrolysis) or increases entropy (such as water exclusion during dimerisation). In isolation protein stays in its lowest energy conformation(s).
The most stable configuration G = 0, if the configuration of the protein tends to change is that G> 0, however it all depends on the medium in which it finds the protein. On the other hand in computational chemistry speaks ineracción energy of protein-ligand, and higher affinity, we talk of G
Change in Gibbs free energy determines whether the process is advantageous and the product is more stable (deltaG0). Usually in a real protein, if conformational changes occur, you would expect deltaG
I suppose that you refer to DG as the difference of the unfolded and folded state of the protein. More conformational changes in the folded structure increases the entropy content of the folded structure and reduces the entropy difference DS of the unfolded and folded state. As DG=DH - TxDS a smaller DS value leads to a flatter slope in the DG plot versus temperature close to the melting temperature and thus increases thermal stability of the protein. This is called entropic stabilisation.
you just check out this article:
Protein Engineering vol. 16 no. 9 pp. 665±671, 2003
DOI: 10.1093/protein/gzg083
When the H2O Gibbs free energy (Gibbs free energy absence of denaturant agent) is more positive, the stability of structure is higher.
There exist a close relationship between protein function and structure, which is mediated by the energetics. Proteins are packed macromolecules, with atoms and a large number of noncovalent atoms which strongly interact, which define the 3D structure, stability, but also the function. There exist many research articles which study relationship between energetics, stability and structure, however, not much has been said about relationship between protein stability and function.
Proteins may undergo large conformations changes during the function performance, with properties which will be defined by energetics and from the way in which stabilizing interactions are defined by the structure. Therefore, we can say that interactions, and so the energetics (binding energies) will determine the stability, structure, but also identify the domains of the proteins which may undergo large conformations changes.
Given that the free energy is a property of the molecule ensembles which populate the equilibrium, the most important point before any consideration is that the two states (1 and 2), represented by the starting point and the final point of your conformational transition, must be reversible otherwise the equilibrium thermodynamics is not applicable as it follows. It is often of interest to evaluate differences in conformational stability among proteins that vary in structure for a conformational change or a single mutation or from chemical modification (or other). Following an instrumental observable (fluorescence, UV to CD, near UV CD, second derivative spectroscopy, etc.), you can denature the protein with sufficient accuracy by means of urea from the initial to the final state of the transition. The midpoints of the urea ([urea]1/2) unfolding curves can be easily determined according the usual methodology of free energy calculation. If the transition curves are steep and parallel, these values are, if different, already indicative of free energy difference. It is important to note that they are independent of the unfolding mechanisms. The free energy for each transition can be determined by ΔG = - RT ln K; where K = [ObsF – Obs]/[Obs – ObsU]. In details, ObsF is the value of the observable at the starting point; ObsU the value at the final point, and Obs the experimental values observed during the transition). In this way it is possible to evaluate the Δ(ΔG) (= ΔG1 – ΔG2) between the two states. Another easy way to determine the Δ(ΔG) is by urea gradient gel electrophoresis, with results comparable to the urea method. Note that the urea method is applicable if you have a two states equilibrium (characterized by very steeps transitions). Whereas transitions are broad you must suspect the presence of other species at equilibrium. In this case we have another story that is much more complex to solve. The structural meaning is explained in earlier answers.
Can any one suggest how we can calculate Gibbs energy change due to change in Phi-Psi angles?
I notice some conceptual confusion. A good basic chemical text for the first year of university is the first aid. The chapter to read is that of the chemical equilibrium of the solutions and thermodynamic relationships that regulate them.
The principles of chemical equilibrium of the solutions are basically the same also for protein solutions. The fundamental condition for using these laws (including thermodynamics) is that the system (that is, the solution and its components) must be at equilibrium, that is, the ratio between the various components of the global reaction (reagents and products, for proteins, native and denatured populations) that are physically present in the test tube at fixed conditions do not change in time. When this happens, we can start to study the equilibrium properties of that reaction, in terms of percentages of denatured and native species.
Of course, the system must be reversible and in the case of proteins we must have at equilibrium a two-state system (only native and denatured species), at least for simple cases. Life becomes much more complicated if we have more than two states at equilibrium (for example intermediate structural forms, at equilibrium).
The thing to keep in mind is that at equilibrium we have always to do with populations of molecules (even for proteins) and the law of mass action describes the average statistic properties of this system and how it is regulated by factors such as temperature, pH, pressure, concentration changes, and so on. And the law of classic thermodynamics that control it, is ΔH - TΔS = ΔG = - RT ln Keq (where most of the relationships used to study properties and behavior of protein solutions come from).
In the case of proteins, mean statistical properties means that we do not follow the denaturation of a single molecule but the percentages of denaturation existing within the entire population of molecules present in the test tube during, for example, the denaturation (at increasing concentrations of urea or GdnHCl). So, thinking of studying the molecular mechanism through which the structure of a single protein is denatured, is not the subject of chemical equilibrium but of the chemical kinetics. With thermodynamics we give a quantitative assessment to the equilibrium under study. That's all, in a very simple and quick way, but if these concepts are not present in the mind, it is useless to read books on the thermodynamics of protein denaturation. Free energy is the quantitative measure that describes the relationship between the populations of denatured and native molecules
Free energy is the quantitative measure that describes the relationship between the populations of denatured and native molecules, whose value depends on other factors such as the variation of enthalpy (the amount of heat in play) and the variation of entropy (generically the level of Disorder in play) which, in turn, describe deeper aspects of the denaturation of a protein solution (for example, enthalpy or entropy driven ), and so on. Do not be discouraged because it is fascinating for protein folding studies, though the most interesting proteins are no longer globular ones, but those that can carry a huge number of biological functions (even hundreds), ie intrinsically denatured proteins (IDPs).
good job.
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