Aqueous solution interactions with sex hormone-binding globulin and estradiol: A theoretical investigation

TL;DR

This theoretical study uses molecular dynamics and docking to explore how aqueous solutions, especially glucose, interact with sex hormone-binding globulin (SHBG) and estradiol (E2), revealing significant interactions affecting binding energies and molecular behavior.

Contribution

The paper introduces a detailed computational analysis of how salts and glucose influence SHBG and E2 interactions, highlighting effects on binding energy and molecular clustering.

Findings

Glucose shows strong interaction with SHBG surface.

Solute components tend to cluster around SHBG.

No significant change in SHBG-E2 binding energy due to solution.

Abstract

Sex hormone-binding globulin (SHBG) is a binding protein that regulates availability of steroids hormones in the plasma. Although best known as steroid carrier, studies have associated SHBG in modulating behavioral aspects related to sexual receptivity. Among steroids, estradiol (17\b{eta}-estradiol, oestradiol or E2) is well recognized as the most active endogenous female hormone, exerting important roles in reproductive and nonreproductive functions. Thus, in this study we aimed to employ molecular dynamics (MD) and docking techniques for quantifying the interaction energy between a complex aqueous solution, composed by different salts, SHBG and E2. Due to glucose concentration resembles those observed in diabetic levels, special emphasis was devoted to uncover the main consequences of this carbohydrate on the SHBG and E2 molecules. We also examined possible energetic changes due to solution on the binding energy of SHBG-E2 complex. In this framework, our calculations uncovered a remarkable interaction energy between glucose and SHBG surface. Surprisingly, we also observed solute components movement toward SHBG yielding clusters surrounding the protein. This finding, corroborated by the higher energy and shorter distance found between glucose and SHBG, suggests a scenario in favor of a detainment state. In addition, in spite of protein superficial area increment it does not exerted modification on binding site area nor over binding energy SHBG-E2 complex. Finally, our calculations also highlighted an interaction between E2 and glucose when the hormone was immersed in the solution. In summary, our findings contribute for a better comprehension of both SHBG and E2 interplay with aqueous solution components.