Dataset Information

Rapid estimation of hydration thermodynamics of macromolecular regions.

ABSTRACT: This work describes a novel protocol to efficiently calculate the local free energy of hydration of specific regions in macromolecules. The method employs Monte Carlo simulations in the grand canonical ensemble to generate water configurations in a selected spherical region in the macromolecule. Excess energy and entropy of hydration are calculated by analyzing the water configurational distributions following the recently published grid inhomogeneous solvation theory method [C. N. Nguyen, T. K. Young, and M. K. Gilson, J. Chem. Phys. 137, 044101 (2012)]. Our method involves the approximations of treating the macromolecule and distant solvent as rigid and performing calculations on multiple such conformations to account for conformational diversity. These approximations are tested against water configurations obtained from a molecular dynamics simulation. The method is validated by predicting the number and location of water molecules in 5 pockets in the protein Interleukin-1? for which experimental water occupancy data are available. Free energy values are validated against decoupling free energy perturbation calculations. The results indicate that the approximations used in the method enable efficient prediction of free energies of water displacement.

SUBMITTER: Raman EP

PROVIDER: S-EPMC3751957 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Rapid estimation of hydration thermodynamics of macromolecular regions.

Raman E Prabhu EP MacKerell Alexander D AD

The Journal of chemical physics 20130801 5

This work describes a novel protocol to efficiently calculate the local free energy of hydration of specific regions in macromolecules. The method employs Monte Carlo simulations in the grand canonical ensemble to generate water configurations in a selected spherical region in the macromolecule. Excess energy and entropy of hydration are calculated by analyzing the water configurational distributions following the recently published grid inhomogeneous solvation theory method [C. N. Nguyen, T. K. ...[more]

PMID: 23927290

Similar Datasets

Project description:Actomyosin is an important molecular motor, and the binding of actin and myosin is an essential research target in biophysics. Nevertheless, the physical factors driving or opposing the binding are still unclear. Here, we investigate the role of water in actin-myosin binding using the most reliable statistical-mechanical method currently available for assessing biomolecules immersed in water. This method is characterized as follows: water is treated not as a dielectric continuum but as an ensemble of molecules; the polyatomic structures of proteins are taken into consideration; and the binding free energy is decomposed into physically insightful entropic and energetic components by accounting for the hydration effect to its full extent. We find that the actin-myosin binding brings large gains of electrostatic and Lennard-Jones attractive interactions. However, these gains are accompanied by even larger losses of actin-water and myosin-water electrostatic and LJ attractive interactions. Although roughly half of the energy increase due to the losses is cancelled out by the energy decrease arising from structural reorganization of the water released upon binding, the remaining energy increase is still larger than the energy decrease brought by the gains mentioned above. Hence, the net change in system energy is positive, which opposes binding. Importantly, the binding is driven by a large gain of configurational entropy of water, which surpasses the positive change in system energy and the conformational entropy loss occurring for actin and myosin. The principal physical origin of the large water-entropy gain is as follows: the actin-myosin interface is closely packed with the achievement of high shape complementarity on the atomic level, leading to a large increase in the total volume available to the translational displacement of water molecules in the system and a resultant reduction of water crowding (i.e., entropic correlations among water molecules).

Project description:The swelling capacity and stability of clay play a crucial role in various areas ranging from cosmetics to oil extraction; hence change in their swelling behaviour after cation exchange with the surrounding medium is important for their efficient utilisation. Here we focus on understanding the role of different hydration properties of cation on the thermodynamics of clay swelling by water adsorption. We have used mica as the reference clay, Na[Formula: see text], Li[Formula: see text], and H[Formula: see text] ions as the interstitial cations, and performed grand canonical Monte Carlo simulations of water adsorption in mica pores (of widths [Formula: see text] Å). The disjoining pressure ([Formula: see text]), swelling free energy ([Formula: see text]), and several structural properties of confined water and ions were calculated to perform a thermodynamic analysis of the system. We expected higher water density in H-mica pores ([Formula: see text]) due to the smaller size of [Formula: see text] ions having higher hydration energy. However, the counter-intuitive trend of [Formula: see text] (bulk density) [Formula: see text] was observed due to adsorption energy, where the interaction of water with mica framework atoms was also found to be significant. All three mica systems exhibited oscillatory behaviour in the [Formula: see text] and [Formula: see text] profiles, diminishing to zero for [Formula: see text] Å. The [Formula: see text] for Na-mica is characterised by global minima at [Formula: see text] corresponding to crystalline swelling with significant and multiple barriers for crystalline swelling to osmotic swelling ([Formula: see text] Å). A shift in the location of global minima of [Formula: see text] towards the higher d values and [Formula: see text] becoming more repulsive is observed in the increasing order of hydration energy of [Formula: see text], [Formula: see text], and [Formula: see text] ions. The [Formula: see text] for all d in the H-mica system thus favours osmotic swelling. We found that the Na[Formula: see text] ions hydrate more surface oxygens, act as anchors, and hold the mica pore together (at smaller d), by sharing hydrating water with ions of the opposite side, forming an electrostatically connected mica-Na-water-Na-mica bridge. The Li[Formula: see text] ions do hydrate surface oxygen atoms, albeit in lesser numbers, and sharing of hydration shell with nearby Li[Formula: see text] ions is also minimum. Hydration by surface atoms and water sharing, both, are minimum in the H[Formula: see text] ion case, as they are mostly present in the center of the pore as diffusive ions, thus exerting a consistent osmotic pressure on the mica frameworks, favouring swelling.

Dataset Information

Rapid estimation of hydration thermodynamics of macromolecular regions.

Publications

Rapid estimation of hydration thermodynamics of macromolecular regions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets