Molecular simulations play important roles in computer-aided drug design (CADD). Especially, these calculations are useful for the analyses of 3D structures of biopolymers, such as proteins, nucleic acids or sugar chains, in structure-based drug design (SBDD) trials. The molecular dynamics (MD) simulation is most widely used for the molecular simulations of biopolymers, and it plays significant...

In this article, we systematically apply a novel implicit-solvent model, the variational implicit-solvent model (VISM) together with the Coulomb-Field Approximation (CFA), to calculate the hydration free energy of a large set of small organic molecules. Because these molecules have been studied in detail by molecular dynamics simulations and other implicit-solvent models, they provide a good be...

The folding kinetics of a seven-residue long alanine polypeptide are investigated using a fully atomic protein model and molecular dynamics simulations. The peptide adopts helical conformations in the native state when simulated in two different implicit solvents: a model with a distance dependent dielectric constant and the generalized Born (GB) model. Although the two solvation models correct...

We present an overview of the recent progress that has been made in understanding the origin of hydrophobic interactions. We discuss the different character of the solvation behaviour of apolar solutes at small and large length scales. We emphasize that the crossover in the solvation behaviour arises from a collective effect, which means that implicit solvent models should be used with care. We...

We compare local and nonlocal dielectric models for the electric potential around a solute. We choose a water molecule as solute so that the comparisons can be related to the behavior of bulk water. We see that, near the solute, the two models give predictions that differ by an order of magnitude, although the difference diminishes away from the solute. We also compare the two models for the pr...

Accelerated molecular dynamics is used to explore the binding of Zn N-terminal fragment amyloid-β, and test performance AMBER-style forcefields. • AMBER forcefield reproduces NMR structure Zn(II) bound Aβ. Implicit solvent performs at least as well explicit in this regard. MD shows subtle difference for different modes. Free energy surface restriction size flexibility due Zn-binding. We report ...

We show how Monte Carlo and related methods as complete enumeration can help to predict and understand the outcomes of concrete biophysical experiments. Three examples are discussed: the eeect of glycosylation on conformational distributions of peptides, the folding of an-helical hairpin model protein, and the structure of a longer cycloamy-lose. One of the major factors hampering the use of Mo...

We present a method to derive implicit solvent models of electrolyte solutions from all-atom descriptions; providing analytical expressions of the thermodynamic and structural properties of the ions consistent with the underlying explicit solvent representation. Effective potentials between ions in solution are calculated to perform perturbation theory calculations, in order to derive the best ...