HLA genotype affects response: Immunotherapy works by activating the patient's own immune system to fight cancer. For effective tumor killing, CD8 ⁺ T cells recognize tumor peptides presented by human leukocyte antigen class I (HLA-I) molecules. In humans, there are three major HLA-I genes ( HLA-A, HLA-B , and HLA-C ). Chowell et al. asked whether germline HLA-I genotype influences how T cells recognize tumor peptides and respond to checkpoint inhibitor immunotherapies (see the Perspective by Kvistborg and Yewdell). They examined more than 1500 patients and found that heterozygosity at HLA-I loci was associated with better survival than homozygosity for one or more HLA-I genes. Thus, specific HLA-I mutations could have implications for immune recognition and for the design of epitopes for cancer vaccines and immunotherapies. Science , this issue p. 582 ; see also p. 516

With the potential wide uses of nanoparticles such as carbon nanotubes in biomedical applications, and the growing concerns of nanotoxicity of these engineered nanoparticles, the importance of nanoparticle–protein interactions cannot be stressed enough. In this study, we use both experimental and theoretical approaches, including atomic force microscope images, fluorescence spectroscopy, CD, SDS-PAGE, and molecular dynamics simulations, to investigate the interactions of single-wall carbon nanotubes (SWCNTs) with human serum proteins, and find a competitive binding of these proteins with different adsorption capacity and packing modes. The π - π stacking interactions between SWCNTs and aromatic residues (Trp, Phe, Tyr) are found to play a critical role in determining their adsorption capacity. Additional cellular cytotoxicity assays, with human acute monocytic leukemia cell line and human umbilical vein endothelial cells, reveal that the competitive bindings of blood proteins on the SWCNT surface can greatly alter their cellular interaction pathways and result in much reduced cytotoxicity for these protein-coated SWCNTs, according to their respective adsorption capacity. These findings have shed light toward the design of safe carbon nanotube nanomaterials by comprehensive preconsideration of their interactions with human serum proteins.

The mechanism of denaturation of proteins by urea is explored by using all-atom microseconds molecular dynamics simulations of hen lysozyme generated on BlueGene/L. Accumulation of urea around lysozyme shows that water molecules are expelled from the first hydration shell of the protein. We observe a 2-stage penetration of the protein, with urea penetrating the hydrophobic core before water, forming a “dry globule.” The direct dispersion interaction between urea and the protein backbone and side chains is stronger than for water, which gives rise to the intrusion of urea into the protein interior and to urea's preferential binding to all regions of the protein. This is augmented by preferential hydrogen bond formation between the urea carbonyl and the backbone amides that contributes to the breaking of intrabackbone hydrogen bonds. Our study supports the “direct interaction mechanism” whereby urea has a stronger dispersion interaction with protein than water.

Noble metal-based nanomaterials have shown promise as potential enzyme mimetics, but the facet effect and underlying molecular mechanisms are largely unknown. Herein, with a combined experimental and theoretical approach, we unveil that palladium (Pd) nanocrystals exhibit facet-dependent oxidase and peroxidase-like activities that endow them with excellent antibacterial properties via generation of reactive oxygen species. The antibacterial efficiency of Pd nanocrystals against Gram-positive bacteria is consistent with the extent of their enzyme-like activity, that is {100}-faceted Pd cubes with higher activities kill bacteria more effectively than {111}-faceted Pd octahedrons. Surprisingly, a reverse trend of antibacterial activity is observed against Gram-negative bacteria, with Pd octahedrons displaying stronger penetration into bacterial membranes than Pd nanocubes, thereby exerting higher antibacterial activity than the latter. Our findings provide a deeper understanding of facet-dependent enzyme-like activities and might advance the development of noble metal-based nanomaterials with both enhanced and targeted antibacterial activities.

The folding free energy landscape of the C-terminal β hairpin of protein G has been explored in this study with explicit solvent under periodic boundary condition and oplsaa force field. A highly parallel replica exchange method that combines molecular dynamics trajectories with a temperature exchange Monte Carlo process is used for sampling with the help of a new efficient algorithm P3ME/RESPA. The simulation results show that the hydrophobic core and the β strand hydrogen bond form at roughly the same time. The free energy landscape with respect to various reaction coordinates is found to be rugged at low temperatures and becomes a smooth funnel-like landscape at about 360 K. In contrast to some very recent studies, no significant helical content has been found in our simulation at all temperatures studied. The β hairpin population and hydrogen-bond probability are in reasonable agreement with the experiment at biological temperature, but both decay more slowly than the experiment with temperature.