Molecular Mechanisms of Functional Modulation of Transcriptional Coactivator PC4 via Phosphorylation on Its Intrinsically Disordered Region.

To investigate the effects of phosphorylation on the function of the human positive cofactor 4 (PC4), an enhanced molecular dynamics (MD) simulation was performed. The simulation system consists of the N-terminal intrinsic disordered region (IDR) of PC4 and a complex that comprises the C-terminal acidic activation domain of a herpes simplex virion protein 16 (VP16ad) and a homodimer of the C-terminal structured core domain of PC4 (PC4ctd). An earlier report of an experimental study reported that the PC4-VP16ad interaction is modulated by incremental phosphorylation of the IDR.

Carbon nanotube recognition by human Siglec-14 provokes inflammation.

For the design and development of innovative carbon nanotube (CNT)-based tools and applications, an understanding of the molecular interactions between CNTs and biological systems is essential. In this study, a three-dimensional protein-structure-based in silico screen identified the paired immune receptors, sialic acid immunoglobulin-like binding lectin-5 (Siglec-5) and Siglec-14, as CNT-recognizing receptors. Molecular dynamics simulations showed the spatiotemporally stable association of aromatic residues on the extracellular loop of Siglec-5 with CNTs.

Extended ensemble simulations of a SARS-CoV-2 nsp1-5'-UTR complex.

Nonstructural protein 1 (nsp1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a 180-residue protein that blocks translation of host mRNAs in SARS-CoV-2-infected cells. Although it is known that SARS-CoV-2's own RNA evades nsp1's host translation shutoff, the molecular mechanism underlying the evasion was poorly understood. We performed an extended ensemble molecular dynamics simulation to investigate the mechanism of the viral RNA evasion.

All-Atom Molecular Dynamics Elucidating Molecular Mechanisms of Single-Transmembrane Model Peptide Dimerization in a Lipid Bilayer.

Protein-protein interactions between transmembrane helices are essential elements for membrane protein structures and functions. To understand the effects of peptide sequences and lipid compositions on these interactions, single-molecule experiments using model systems comprising artificial peptides and membranes have been extensively performed. However, their dynamic behavior at the atomic level remains largely unclear.

GA-guided mD-VcMD: A genetic-algorithm-guided method for multi-dimensional virtual-system coupled molecular dynamics.

We introduced a conformational sampling method in an earlier report: The multi-dimensional virtual-system coupled molecular dynamics (mD-VcMD) enhances conformational sampling of a biomolecular system by computer simulations. Herein, new sampling method, a subzone-based mD-VcMD, is presented as an extension of mD-VcMD. Then, the subzone-based method is extended further using a genetic algorithm (GA) named the GA-guided mD-VcMD.

Tim4 recognizes carbon nanotubes and mediates phagocytosis leading to granuloma formation.

Macrophage recognition and phagocytosis of crystals is critical for the associated fibrosis and cancer. Of note, multi-walled carbon nanotubes (MWCNTs), the highly representative products of nanotechnology, induce macrophage NLRP3 inflammasome activation and cause asbestosis-like pathogenesis. However, it remains largely unknown how macrophages efficiently recognize MWCNTs on their cell surfaces.