Polyethylene glycol (PEG) is a non-ionic water soluble polymer that is used as an additive in protein solutions to induce protein crystallization. PEG in dilute solution concentrations and within a molecular weight range, induces an attractive protein-protein interaction. However the strength of this attractive proteinprotein interaction weakens with increasing PEG concentration and molecular w...

Predicting solvation free energies and describing the complex water behavior that plays an important role in essentially all biological processes is a major challenge from the computational standpoint. While an atomistic, explicit description of the solvent can turn out to be too expensive in large biomolecular systems, most implicit solvent methods fail to capture "dewetting" effects and heter...

The principle of group additivity is a standard feature of analyses of the energetics of protein folding, but it is known that it may not always be valid for the polar peptide group. The neighboring residue effect shows that group additivity is not strictly valid for a heteropeptide. We show here that group additivity fails seriously for peptide groups close to either peptide end, even for a ho...

Force field accuracy is still one of the "stalemates" in biomolecular modeling. Model systems with high quality experimental data are valuable instruments for the validation and improvement of effective potentials. With respect to protein-ligand binding, organic host-guest complexes have long served as models for both experimental and computational studies because of the abundance of binding af...

The octanol-water partition coefficient (logPow) is an important index for measuring solubility, membrane permeability, and bioavailability in the drug discovery field. In this paper, the logPow values of 58 compounds were predicted by alchemical free energy calculation using molecular dynamics simulation. In free energy calculations, the atomic charges of the compounds are always fixed. Howeve...

Internet Electron. J. Mol. Des. 2003, 1, 000–000 Abstract In order to separate the effect of substituents into two parts, referring to the interaction of the reacting molecules and the solvation, the δ∆G, δ∆H and δ∆S reaction constants were defined and determined from the dependence of ∆G, ∆H and ∆S activation parameters on the σ substituent constants, by analogy with the Hammett equation. The ...

The computation of distribution coefficients between polar and apolar phases requires both an accurate characterization of transfer free energies between phases and proper accounting of ionization and protomerization. We present a protocol for accurately predicting partition coefficients between two immiscible phases, and then apply it to 53 drug-like molecules in the SAMPL5 blind prediction ch...

3.2. Energy Minimization 1592 3.3. Adiabatic Mapping 1593 3.4. Molecular Dynamics 1593 3.4.1. Simulated Environment 1595 3.4.2. SHAKE 1595 3.4.3. Experimental Conditions 1596 3.4.4. Solvation 1596 3.5. Langevin Dynamics 1597 3.6. Brownian Dynamics 1597 3.7. Monte Carlo 1598 3.8. Simulated Annealing 1598 3.9. Nondynamic Methods 1598 3.9.1. Conformational Sampling 1598 3.9.2. Principal Component ...

The development and parameterization of a solvent potential of mean force designed to reproduce the hydration thermodynamics of small molecules and macromolecules aimed toward applications in conformation prediction and ligand binding free energy prediction is presented. The model, named SGB/NP, is based on a parameterization of the Surface Generalized Born continuum dielectric electrostatic mo...

Factor Xa (fXa) is a promising target for antithrombotic drugs. Recently, we presented a molecular dynamics study on fXa, which highlighted the need for a careful system setup to obtain stable simulations. Here, we show that these simulations can be used to predict the free energy of binding of several fXa inhibitors. We tested molecular mechanics/Poisson-Boltzmann surface area, molecular mecha...