ABSTRACT
In this paper, we present a computational study of the dynamics of the potent anti-HIV virucidal protein cyanovirin in complex with mannose disaccharides. Recently, it has been experimentally demonstrated that cyanovirin binds mannose oligomers on the surface of glycoprotein gp120. gp120, a protein on the surface of the HIV virus, is key in the process of viral docking and transfer of genetic material into human cells. Cyanovirin prevents the transfer of viral RNA into human cells. In this study, we found that, among all residues that show nuclear Overhauser effects in the solution NMR experiments, residues Glu41 and Arg76 appear to interact with the sugar at the high-affinity binding site through stronger Coulombic interactions. In particular, Arg76 participates in a dynamical mechanism that caps and locks the sugar once it is bound to the protein. We also studied the distribution of glycosidic torsional angles of mannose disaccharides in solution and compared it with those when bound at the high- and low-affinity sites of the protein. Throughout our 20 ns simulations, we find that the sugar bound to the high-affinity site preserves the most favorable conformation in solution while the sugar bound at the low-affinity site does not. The sugar at the low-affinity site can adopt both conformations, but we find it most predominantly on the one that is least probable for the free sugar in solution. We also carried out a detailed study of the interactions between the disaccharides and different amino acids as well as between the disaccharide and the solvent at both binding locations.
Subject(s)
Anti-HIV Agents/chemistry , Bacterial Proteins/chemistry , Carrier Proteins/chemistry , Disaccharides/chemistry , Mannose/chemistry , Arginine/chemistry , Binding Sites , Glutamic Acid/chemistry , HIV Envelope Protein gp120/chemistry , Humans , Hydrogen Bonding , Magnetic Resonance Spectroscopy , Models, Chemical , Molecular Conformation , Software , ThermodynamicsABSTRACT
In this paper we investigate the transient photoelectron spectrum of I2(-) in CO2 clusters recently measured by Neumark and co-workers. This work reveals a rich excited state dynamics with various competing electronic output channels. We find good agreement with experiments and we are able to relate the transient signal to different dynamical events that occur during the evolution of the cluster and its fragmentation products.
ABSTRACT
A molecular dynamics study of the depletion of water (drying) around a single and between two hydrophobic nanoscale oblate plates in explicit water as a function of the distance of separation between them, their size, and the strength of the attraction between the plates and the water molecules is presented. A simple macroscopic thermodynamic model based on Young's law successfully predicts drying between the stacked plates and accounts for the free-energy barriers to this drying. However, because drying around a single plate is not macroscopic, a molecular theory is required to describe it. The data are consistent with the rate-determining step in the hydrophobic collapse of the two plates being a large-scale drying fluctuation, characterized by a free-energy barrier that grows with particle size.
