Molecular dynamics simulations elucidate conformational selection and induced fit mechanisms in the binding of PD-1 and PD-L1.

PD-L1 and PD-L2 differ in their molecular mechanisms of interaction with PD-1.

The programmed death-1 (PD-1) molecule is involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. PD-1 interacts with two ligands, PD-L1 and PD-L2. We have investigated the molecular mechanisms of PD-1 interactions with its ligands by surface plasmon resonance and cell surface binding as well as the ability of the two ligands to compete f...

A Role for Both Conformational Selection and Induced Fit in Ligand Binding by the LAO Protein

Molecular recognition is determined by the structure and dynamics of both a protein and its ligand, but it is difficult to directly assess the role of each of these players. In this study, we use Markov State Models (MSMs) built from atomistic simulations to elucidate the mechanism by which the Lysine-, Arginine-, Ornithine-binding (LAO) protein binds to its ligand. We show that our model can p...

Over-Expression of Immunosuppressive Molecules, PD-L1 and PD-L2, in Ulcerative Colitis Patients

Size Dependence of the Elastic Properties of Pd Nanowire: Molecular Dynamics Simulation

The mechanical properties including elastic stiffness constants as well as bulk modulus of Palladium (Pd) nanowire were calculated in the constant temperature and pressure (NPT), ensemble by molecular dynamics (MD) simulation technique. The quantum Sutton-Chen (Q-SC) many-body potential was used to calculate the cohesive energy as well as forces experience by every atoms. The temperature and pr...

Producing Soluble Human Programmed Cell Death Protein-1: A Natural supporter for CD4+T cell Cytotoxicity and Tumor Cells Apoptosis

Background: Programmed cell death protein-1 (PD-1)/PD-L1 pathway is one of the immune checkpoint pathways involved in regulation of the immune responses and suppression of anti-tumor defense. PD-1/B7-H1-blocking antibodies improve immune responses such as cytotoxic activity of CD8+/CD4+T cells and also increase mortality of tumor cells; however their use is accompanied by adverse effects in pat...