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Different approaches for treating the solvent in biophysical simulations are reviewed. They include explicit atomistic (classical fixed‐charge, polarizable, or ab initio), explicit coarse‐grained (polarizable or not), and implicit approaches (dielectric‐based or empirical). The solvent is usually an aqueous electrolyte solution, but it can also be an aqueous mixture or heterogeneous, as in micelles and lipid bilayers. The treatment of the solvent is tied to that of the solute, with implicit solvation exhibiting the highest versatility. Applications of implicit and coarse‐grained solvent modeling include a wide range of biological processes, such as protein folding, ligand binding, lipid self‐assembly, and transmembrane translocation. The advantages and disadvantages of each approach are discussed and thoughts are offered on the optimal choice of method for different problems.

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Several membrane proteins and numerous membrane-active peptides have been studied in detergent micelles by solution NMR. However, the detailed structure of these complexes remains unknown. We propose a modeling approach that treats the protein and detergent in atomistic detail and the solvent implicitly. The model is based on previous work on dodecylphosphocholine micelles, adapted for use with the CHARMM36 force field and extended to sodium dodecyl sulfate micelles. Solvation parameters were slightly adjusted to reproduce experimental data on aggregation numbers and critical micelle concentrations. To test the approach, several membrane-active peptides and three β-barrel membrane proteins were subjected to molecular dynamics simulations in the presence of a large number of detergent molecules. Their experimentally determined secondary structure was maintained and the RMSD values were less than 2 Å. Deformations were commonly observed in the N or C termini. The atomistic view of the protein-micelle systems that this approach provides could be useful in interpreting biophysical experiments carried out in the presence of detergent.

prefers to open to the intermediate and large conductance states. In the presence of the willardiine partial agonists, the channel opens more frequently to the smallest and intermediate conductance states. Kinetic modeling using maximum interval likelihood rate optimization revealed two time constants in each open state and at least three in the closed state for the partial and the full agonists. These data suggest the mode of channel activation is similar for both glutamate and willardiine compounds with varying rates of activation. Supported by NIH NS049223.