A statistical thermodynamic development is given of a new implicit solvent model that avoids the traditional system size limitations of computer simulation of macromolecular solutions with periodic boundary conditions. This implicit solvent model is based upon the quasi-chemical approach, distinct from the common integral equation trunk of the theory of liquid solutions. The idea is geometrical...

The motion of a biomolecule greatly depends on the engulfing solution, which is mostly water. Instead of representing individual water molecules, it is desirable to develop implicit solvent models that nevertheless accurately represent the contribution of the solvent interaction to the motion. In such models, hydrophobicity is expressed as a weighted sum of atomic surface areas. The derivatives...

Implicit solvent models are powerful tools in accounting for the aqueous environment at a fraction of the computational expense of explicit solvent representations. Here, we compare the ability of common implicit solvent models (TC, OBC, OBC2, GBMV, GBMV2, GBSW, GBSW/MS, GBSW/MS2 and FACTS) to reproduce experimental absolute hydration free energies for a series of 499 small neutral molecules th...

Version 9 of the Amber simulation programs includes a new semi-empirical hybrid QM/MM functionality. This includes support for implicit solvent (generalized Born) and for periodic explicit solvent simulations using a newly developed QM/MM implementation of the particle mesh Ewald (PME) method. The code provides sufficiently accurate gradients to run constant energy QM/MM MD simulations for many...

We present a new hybrid explicit/implicit solvent method for dynamics simulations of macromolecular systems. The method models explicitly the hydration of the solute by either a layer or sphere of water molecules, and the generalized Born (GB) theory is used to treat the bulk continuum solvent outside the explicit simulation volume. To reduce the computational cost, we implemented a multigrid m...

The assumption that similar structures have similar folding probabilities (p(fold)) leads naturally to a procedure to evaluate p(fold) for every snapshot saved along an equilibrium folding-unfolding trajectory of a structured peptide or protein. The procedure utilizes a structurally homogeneous clustering and does not require any additional simulation. It can be used to detect multiple folding ...

Recent studies have shown that explicit solvent molecular dynamics (MD) simulation followed by structural averaging can consistently improve protein structure models. We find that improvement upon averaging is not limited to explicit water MD simulation, as consistent improvements are also observed for more efficient implicit solvent MD or Monte Carlo minimization simulations. To determine the ...

The treatment of hydration effects in protein dynamics simulations varies in model complexity and spans the range from the computationally intensive microscopic evaluation to simple dielectric screening of charge-charge interactions. This paper compares different solvent models applied to the problem of estimating the free-energy difference between two loop conformations in acetylcholinesterase...