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Previous research has shown that the major toxicity mechanism for many environment chemicals is binding with estrogen receptor (ER) and blocking endogenous estrogen access, including bisphenol A (BPA). However, the molecular level understanding the global consequence of BPA binding on the full-length architectures of ER is largely unknown, which is a necessary stage to evaluate estrogen-like toxicity of BPA. In the present work, the consequence of BPA on full-length architectures of ER was firstly modeled based on molecular dynamics, focusing on the cross communication between multi-domains including ligand binding domain (LBD) and DNA binding domain (DBD). The study proved consequence of BPA upon full-length ER structure was dependent on long-range communications between multiple protein domains. The allosteric effects occurring in LBD units could alter dimerization formation through a crucial change in residue-residue connections, which resulted in relaxation of DBD. It indicated BPA could present consequence on the full-size receptor, not only on the separate domains, but also on the cross communication among LBD, DBD, and DNA molecules. It might provide detailed insight into the knowledge about the structural characteristics of ER and its role in gene regulation, which eventually helped us evaluate the estrogen-like toxicity upon BPA binding with full-length ER.

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The increasing evidences have suggested that expression of single nucleotide polymorphisms (SNP) coded thyroid hormone receptors (THR) generally are associated with individual susceptibility to chemicals. In the present research, multiple molecular dynamics simulations on four SNP mutants (G332R, T337Δ, G345R, and G347E) were performed to investigate the structural and dynamical altering, which could lead to a binding capability variation to triiodothyronine (T3). It proved the structures of two SNP mutants (G345R and T337Δ) occurring in the THR proteins had experienced conformational change to a great extend, which also led to a significant decreasing in binding ability with T3. In addition, two mutates (G345R and G347E) and wild type THR proteins were expressed and purified based on site-directed mutagenesis technology to test their binding abilities with T3 by fluorescence experiments. The fluorescence quenching efficiencies of two mutates displayed that the conjugation with T3 decreased with a significant rate in G345R system and a little rate in G347E system compared with its wild type. It was consistent with the molecular dynamic research that the SNP mutations did change structures of THR protein, and thereby decreased the binding behavior of T3 at different extent. The overall molecular-level look at the protein structure may provide the structural basis to explain how one amino acid change can create a ripple effect on the protein structures and eventually affect the binding affinity of the ligands, which maybe the first stage to understand how SNP mutation results in individual difference in susceptibility to variant chemicals.

Environmental contextSingle-walled carbon nanotubes can have adverse physiological effects by interacting with proteins. Using serum bovine albumin as a model protein, we investigate the conformational changes in proteins at the tertiary structure level upon interaction with carbon nanotubes. This specific study of a model protein helps our understanding of the general binding mechanisms involved, and allows us to predict the potential adverse effects of carbon nanotubes interacting with other proteins. AbstractConsidering the large-scale production of diversified nanomaterials, it is of paramount importance to unravel the structural details of interactions between nanoparticles and biological systems at the molecular level, with the aim to reveal the potential adverse biological impacts. Herein, with single-walled carbon nanotubes (SWCNTs) acting as model nanomaterials and bovine serum albumin (BSA) acting as a model protein, a combination of spectroscopy experiments and molecular modelling was applied to help us unravel some important issues on the mechanism of protein interactions with SWCNTs. As a result, SWCNTs were first proved to bind at subdomain IB of BSA based on fluorescence experiments and molecular dynamics modelling. In addition, hydrophobic interactions were recognised as the driving force governing the binding behaviour between the SWCNTs and BSA. As a consequence, SWCNT binding led to a conformational change both at the secondary and tertiary structure levels. Insight into the binding details between BSA and SWCNT can help understand the recognition mechanism between SWCNTs and proteins, thus be helpful to predict the potential adverse effects of SWCNTs.