ABSTRACT
A model for carboxylic acids, in both the protonated and deprotonated states, is developed in which hydrogen interaction sites are not used and all interactions are short-ranged. A method for constant pH simulations, which exploits these features of the model, is developed. The constant pH method samples protonation states by making discrete Monte Carlo steps and is able to efficiently move between states in two steps. The method is applied to the polymer poly(methacrylic acid), a pH-responsive polymer that undergoes structural changes as a function of pH. The model is able to reproduce the structural changes induced by pH.
ABSTRACT
Thermoresponsive polymers can change structure or solubility as a function of temperature. Block co-polymers of polyethers have a response that depends on polymer molecular weight and co-polymer composition. A coarse-grained model for aqueous polyethers is developed and applied to polyethylene oxide and polyethylene oxide-polypropylene oxide-polyethylene oxide triblock co-polymers. In this model, no interaction sites on hydrogen atoms are included, no Coulombic interactions are present, and all interactions are short-ranged, treated with a combination of two- and three-body terms. Our simulations find that The triblock co-polymers tend to associate at temperatures above 350 K. The aggregation is stabilized by contact between The hydrophobic methyl groups on The propylene oxide monomers and involves a large, favorable change in entropy.
ABSTRACT
A model for linear alkanes is presented in which interaction sites are only on the carbon atoms, and the range of the potential is reduced using the Stillinger-Weber potential. The model is optimized for aqueous and liquid alkane properties and can match thermodynamic and structural properties, including solvation free energies, liquid densities, and liquid/vapor and liquid/water surface tensions for alkanes over a range of lengths. The results for long alkanes indicate that such models can be useful as accurate, yet efficient, coarse-grained potentials for macromolecules in water and other environments.
ABSTRACT
Channelrhodopsins (ChR1 and ChR2) are light-activated ion channels that enable photomobility of microalgae from the genus Chlamydomonas. Despite common use of ChR2 in optogenetics for selective control and monitoring of individual neurons in living tissue, the protein structures remain unresolved. Instead, a crystal structure of the ChR chimera (C1C2), an engineered combination of helices I-V from ChR1, without its C-terminus, and helices VI-VII from ChR2, is used as a template for ChR2 structure prediction. Surprisingly few studies have focused in detail on the chimera. Here, we present atomistic molecular dynamics studies of the closed-state, non-conducting C1C2 structure and protonation states. A new and comprehensive characterization of interactions in the vicinity of the gating region of the pore, namely between residues E90, E123, D253, N258, and the protonated Schiff base (SBH), as well as nearby residues K93, T127, and C128, indicates that the equilibrated C1C2 structure with both E123 and D253 deprotonated closely resembles the available crystal structure. In agreement with experimental studies on C1C2, no direct or water-mediated hydrogen bonding between an aspartate and a cysteine (D156-O S-C128) that would define a direct-current gate in C1C2 was observed in our simulations. Finally, we show that a single hydrogen bond between a glutamic acid (E90) and an asparagine (N258) residue suffices to keep the gate of C1C2 closed and to disable free water and ion passage through the putative pore, in contrast to the double bond proposed earlier for ChR2. We anticipate that this work will provide context for studies of both the gating process and water and ion transport in C1C2, and will spark interest in further experimental studies on the chimera.
