Monte Carlo computer simulation of water–amino acid interactions

Goodfellow, Julia M.; Finney, John; Barnes, P.

doi:10.1098/rspb.1982.0005

Cited by 24 publications

(3 citation statements)

References 14 publications

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“…16,17 However, interpretation of the solvent density map is often complicated due to solvent mobility and disorder, and determination of only a limited number of well-ordered solvent sites may be possible. 16,18,19 Theoretical methods such as energy minimization, 20,21 Monte Carlo simulations, 22 and molecular dynamics simulations 15,[23][24][25][26][27][28] have been used for predicting water sites at a protein surface and calculating hydration energies. [29][30][31][32][33][34] In particular, molecular dynamics simulations have been used by several groups [29][30][31][32][33][34] to calculate the change in free energy associated with hydration of a cavity within a protein: the specific methods differ in detail, but essen-tially, the free energy is calculated from the energetic cost of removal of a water molecule from bulk solvent and the energetic gain of insertion of a water molecule into a cavity.…”

Section: Introductionmentioning

confidence: 99%

WATGEN: An algorithm for modeling water networks at protein–protein interfaces

Bui¹,

Schiewe²,

Haworth³

2007

J Comput Chem

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Water molecules at protein-protein interfaces contribute to the close packing of atoms and ensure complementarity between the protein surfaces, as well as mediating polar interactions. Therefore, modeling of interface water is of importance in understanding the structural basis of biomolecular association. We present an algorithm, WATGEN, which predicts locations for water molecules at a protein-protein or protein-peptide interface, given the atomic coordinates of the protein and peptide. A key element of the WATGEN algorithm is the prediction of water sites that can form multiple hydrogen bonds that bridge the binding interface. Trial calculations were performed on water networks predicted by WATGEN at 126 protein-peptide interfaces (X-ray resolutions

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Section: Introductionmentioning

confidence: 99%

WATGEN: An algorithm for modeling water networks at protein–protein interfaces

Bui¹,

Schiewe²,

Haworth³

2007

J Comput Chem

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“…In previous work which investigated structural aspects of water-biomolecule hydrate crystals, we extended the PE model for water (8) to describe water-protein interactions. In this paper, we investigate the extent ofnon-pair-additive effects, using Monte Carlo simulations on a variety ofwater-biomolecule systems.…”

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confidence: 99%

“…The PE model has been extended previously to describe water-amino acid interactions by Goodfellow et at (8). Each solvent-amino acid interaction is described by a set of nonbonded (Lennard-Jones) coefficients together with a set of partial atomic charges centered at each nonhydrogen atom of the amino acid residue.…”

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confidence: 99%

Cooperative effects in water-biomolecule crystal systems.

Goodfellow¹

1982

Proc. Natl. Acad. Sci. U.S.A.

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Monte Carlo computer simulation techniques have been used to model non-pair-additive (cooperative) effects in the water organization around several-biomolecules. Although most models for water assume pair-additive potentials, both quantum mechanical calculations and experimental data indicate that cooperative effects are not negligible in hydrogen-bonded systems such as water. The many-body polarizable electropole (PE) model for water is used to examine the extent and the consequences of this cooperative behavior in-several biomolecule hydrate crystals. Increases in the dipole moments ofwater molecules are predicted in all systems studied so far and can be as much as 50% more than the monomer value of 1.855 debyes. The average value of the individual dipole moments for any one system differs from that of another system and, therefore, should be considered a property of the system and not of the water molecule itself. When this previously calculated average value of the dipole moment for water molecules in a given system is used as a fixed parameter in the simulation, we find differences between this fixed calculation and the original unfixed simulation. An alternative procedure, which allows for a spread in dipole moments and is not dependent on a predetermined average value, has been developed to make simulations of large water-protein systems, including cooperative effects, computationally feasible.Most interatomic potential functions used in energy calculations are of a pairwise form in which it is assumed that many-body effects are either negligible or that they can be accounted for by an effective pairwise function (1). However, it has been found that many-body effects in water are not negligible (2). Both Hankins et al. (3) and Del Bene and Pople (4) found there were non-pair-additive contributions in hydrogen bond formation in the water trimer compared with the water dimer. Campbell and *Mezei (5) have developed a quantum mechanical non-pair-additive model with which they-find large deviations from pairwise additivity in their investigations of various forms of ice. More recently, Clementi et at (6), using sophisticated basis sets, have studied the nonadditivity ofinteractions in the water trimer and have found that the nonadditive contribution is smaller than that calculated previously by Del Bene and Pople (4).Non-pair-additivity is a consequence of many-body interactions at the molecular level and depends on both the properties of the molecule and its environment. The polarizability of the electronic charge is one molecular property that is important in the interactions between water molecules and gives a large contribution to the.high value for the macroscopic property of the static dielectric constant of bulk water. One result of the polarization of water molecules in bulk water is that the dipole moment of each molecule is increased above the value found in the monomer. For example, in hexagonal ice I, the dipole moment was found experimentally to be between 2.6 and 3.0 debyes (D) (7), whic...

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Hydration energy landscape of the active site cavity in cytochrome P450cam

Helms

Wade

1998

Proteins

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Hydration of protein cavities influences protein stability, dynamics, and function. Protein active sites usually contain water molecules that, upon ligand binding, are either displaced into bulk solvent or retained to mediate protein-ligand interactions. The contribution of water molecules to ligand binding must be accounted for to compute accurate values of binding affinities. This requires estimation of the extent of hydration of the binding site. However, it is often difficult to identify the water molecules involved in the binding process when ligands bind on the surface of a protein. Cytochrome P450cam is, therefore, an ideal model system because its substrate binds in a buried active site, displacing partially disordered solvent, and the protein is well characterized experimentally. We calculated the free energy differences for having five to eight water molecules in the active site cavity of the unliganded enzyme from molecular dynamics simulations by thermodynamic integration employing a three-stage perturbation scheme. The computed free energy differences between the hydration states are small (within 12 kJ mol-1) but distinct. Consistent with the crystallographic determination and studies employing hydrostatic pressure, we calculated that, although ten water molecules could in principle occupy the volume of the active site, occupation by five to six water molecules is thermodynamically most favorable.

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Monte Carlo computer simulation of water–amino acid interactions

Cited by 24 publications

References 14 publications

WATGEN: An algorithm for modeling water networks at protein–protein interfaces

WATGEN: An algorithm for modeling water networks at protein–protein interfaces

Cooperative effects in water-biomolecule crystal systems.

Hydration energy landscape of the active site cavity in cytochrome P450cam

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