Question

Write a 1 page scientific review with Introduction, Results, Key findings and Summary on this paper: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5488930/

Answer 1

Protein-ligand interactions which is the basic of many essential life functions is remained center of many pharmaceutical interventions which are generally based upon manipulation of molecular recognition by proteins. In these interactions role played by enthalpy and entropy is very important as both play a crucial role in the thermodynamics of binding. This article demonstrated a way to measure changes in protein conformational entropy using a dynamical proxy provided by NMR relaxation methods. Additionally, the contribution of solvent entropy is also recalibrated.

Authors tested the hypothesis that the entropy meter is universally applicable [i.e., that the scaling between changes in fast internal motion and changes in conformational entropy is constant. They had augmented many of these NMR relaxation studies by measuring the binding thermodynamics using isothermal titration calorimetry (ITC) under corresponding NMR solution conditions (i.e., buffer, pH, temperature). 28 proteins and their complexes were prepared. Some published NMR relaxation and thermodynamic studies were used without further analysis. These protein–ligand complexes are used to show a quantitative relationship between measures of fast side-chain motion and the underlying conformational entropy.

These results provided a comprehensive and unified view of the general role of entropy in high-affinity molecular recognition by proteins. the coefficients which were related to:

1. changes in fast protein side-chain motion to changes in conformational entropy

2. changes in accessible surface area to changes in solvent entropy, and

3. the loss of rotational-translational entropy in high-affinity complexes have been determined.

Authors concluded that the relationship between fast internal side-chain motion and the underlying conformational entropy is universal and represents a fundamental property of soluble proteins. It is demonstrated that conformational entropy has a highly variable role in the formation of complexes involving proteins: It can favor, disfavor, or have no impact on the free energy of binding. There are no obvious structural correlates apparent for this behavior. The connection between structure, the enthalpy that it represents, conformational entropy, and internal motion presents an immediate challenge to our current understanding of protein thermodynamics and function. In this vein, the view emerging from crystallographic analysis of minor conformers in proteins, combined with the dynamical proxy validated here, provides a means to quantify the role of conformational entropy in protein structure and function. This study confirmed that inclusion of conformational entropy is necessary to understanding the origins of high-affinity interactions involving proteins.