Solute-solute solvent-induced interaction: molecular dynamics simulation of a mixed model system in water (original) (raw)
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Solvent-Induced Forces between Two Hydrophilic Groups
The Journal of Physical Chemistry, 1994
Molecular dynamics simulations were used to calculate the force between two simple hydrophilic solutes in dilute aqueous solution. The "solutes" were two water molecules in the same relative orientation as the nextnearest neighbors in hexagonal ice I. Both the direct and solvent-induced contributions to the force were calculated as a function of separation distance. The total force between the solutes was found to be most attractive at 5.0 (-1.6 kcal/mol/A). The potential of mean force had a minimum at 4.3 A, which is 0.2 A closer than the next-nearest-neighbor distance in ice. A parallel set of simulations were conducted with the partial charges on the "solutes" removed to examine hydrophobic analogs. In this case, the total force was most attractive at 3.5 A (-0.9 kcal/mol/A), and the minimum of the potential was at the contact distance of 3.2 A. In agreement with earlier predictions, the maximum solvent-induced contribution to the potential was cu. 4 times more negative for the hydrophilic "solutes" than for the hydrophobic ones. These differences are shown to be due predominantly to a solvent water molecule which simultaneously hydrogen bonds to both hydrophilic "solutes". The results support earlier assertions that solvent-induced interactions between polar amino acid residues are more important in protein folding and stability than generally considered.
Biophysical Journal, 2003
Protein structure and dynamics in nonaqueous solvents are here investigated using molecular dynamics simulation studies, by considering two model proteins (ubiquitin and cutinase) in hexane, under varying hydration conditions. Ionization of the protein groups is treated assuming ''pH memory,'' i.e., using the ionization states characteristic of aqueous solution. Neutralization of charged groups by counterions is done by considering a counterion for each charged group that cannot be made neutral by establishing a salt bridge with another charged group; this treatment is more physically reasonable for the nonaqueous situation, contrasting with the usual procedures. Our studies show that hydration has a profound effect on protein stability and flexibility in nonaqueous solvents. The structure becomes more nativelike with increasing values of hydration, up to a certain point, when further increases render it unstable and unfolding starts to occur. There is an optimal amount of water, ;10% (w/w), where the protein structure and flexibility are closer to the ones found in aqueous solution. This behavior can explain the experimentally known bell-shaped dependence of enzyme catalysis on hydration, and the molecular reasons for it are examined here. Water and counterions play a fundamental and dynamic role on protein stabilization, but they also seem to be important for protein unfolding at high percentages of bound water.
Proteins: Structure, Function, and Genetics, 1996
A system containing the globular protein ubiquitin and 4,197 water molecules has been used for the analysis of the influence exerted by a protein on solvent dynamics in its vicinity. Using Voronoi polyhedra, the solvent has been divided into three subsets, i.e., the first and second hydration shell, and the remaining bulk, which is hardly affected by the protein. Translational motion in the first shell is retarded by a factor of 3 in comparison to bulk. Several molecules in the first shell do not reach the diffusive regime within 100 ps. Shell-averaged orientational autocorrelation functions, which are also subject to a retardation effect, cannot be modeled by a single exponential time law, but are instead well-described by a Kohlrausch-Williams-Watts (KWW) function. The underlying distribution of single-molecule rotational correlation times is both obtained directly from the simulation a n d derived theoretically. The temperature dependence of reorientation is characterized by a strongly varying correlation time, but a virtually temperature-independent KWW exponent. Thus, the coupling of water structure relaxation with the respective environment, which is characteristic of each solvation shell, is hardly affected by temperature. In other words, the functional form of the distributions of singlemolecule rotational correlation times is not subject to a temperature effect. On average, a correlation between reorientation and lifetimes of neighborhood relations is observed.
Physical Review E, 1998
We present a computer simulation picture of the dynamical behavior, at room temperature, of water in the region close to a protein surface. We analyzed the probability distribution of water molecules diffusing near the surface, and we found that it deviates from a Gaussian, which is predicted for Brownian particles. Consistently, the mean square displacements of water oxygens show a sublinear trend with time. Moreover, the relaxation of hydration layers around the whole protein is found to follow a stretched exponential decay, typical of complex systems, which could as well be ascribed to the non-Gaussian shape of the propagator. In agreement with such findings, the analysis of water translational and reorientational diffusion showed that not only are the solvent molecule motions hindered in the region close to the protein surface, but also the very nature of the particle diffusive processes, both translational and rotational, is affected. The deviations from the bulk water properties, which put into evidence a deep influence exerted by the protein on the solvent molecule motion, are discussed in connection with the presence of spatial ͑protein surface roughness͒ and temporal ͑distribution of water residence times͒ disorder inherent in the system.
Collective properties of hydration: long range and specificity of hydrophobic interactions
Biophysical Journal, 1997
We report results of molecular dynamics (MD) simulations of composite model solutes in explicit molecular water solvent, eliciting novel aspects of the recently demonstrated, strong many-body character of hydration. Our solutes consist of identical apolar (hydrophobic) elements in fixed configurations. Results show that the many-body character of PMF is sufficiently strong to cause 1) a remarkable extension of the range of hydrophobic interactions between pairs of solute elements, up to distances large enough to rule out pairwise interactions of any type, and 2) a SIF that drives one of the hydrophobic solute elements toward the solvent rather than away from it. These findings complement recent data concerning SIFs on a protein at single-residue resolution and on model systems. They illustrate new important consequences of the collective character of hydration and of PMF and reveal new aspects of hydrophobic interactions and, in general, of SIFs. Their relevance to protein recognition, conformation, function, and folding and to the observed slight yet significant nonadditivity of functional effects of distant point mutations in proteins is discussed. These results point out the functional role of the configurational and dynamical states (and related statistical weights) corresponding to the complex configurational energy landscape of the two interacting systems: biomolecule + water.
Chemical Physics Letters, 1996
This work concerns solvent-induced interactions and their most familiar subset, hydrophobic interactions. Molecular dynamics simulations allow the eliciting of: (i) the inherently strong non-additivity of solvent-induced forces (SIFs) in water, caused by the failure of Kirkwood's superposition approximation and (ii) the quantitative microscopically space-resolved relation of SIFs to configurational changes of the solvent caused by solutes. These results provide the ground for understanding quantitatively and microscopically many biologically significant findings related to hydration and SIF modulation. Also, they suggest the existence of highly specific solute-solute interactions and of otherwise forbidden pathways for chemical and biological processes in solution, including protein folding and biomolecular recognition. * Accounts of this work were presented at the JRDC-JAREC Symposium on Water Structure and Properties, Kyoto, 1994, at the 2nd IUPAB Symposium on Biological Physics, Mi~nchen, 1995 and at the JRDC-JAREC workshop 'Water and Biological Systems', Tokyo, 1995. Elsevier Science B.V. All rights reserved PII S0009-2614(96)00185-6
Protein Surface Dynamics: Interaction with Water and Small Solutes
Journal of Biological Physics, 2005
Previous time resolved measurements had indicated that protons could propagate on the surface of a protein, or a membrane, by a special mechanism that enhances the shuttle of the proton towards a specific site [1]. It was proposed that a proper location of residues on the surface contributes to the proton shuttling function. In the present study, this notion was further investigated using molecular dynamics, with only the mobile charge replaced by Na + and Cl − ions. A molecular dynamics simulation of a small globular protein (the S6 of the bacterial ribosome) was carried out in the presence of explicit water molecules and four pairs of Na + and Cl − ions. A 10 ns simulation indicated that the ions and the protein's surface were in equilibrium, with rapid passage of the ions between the protein's surface and the bulk. Yet it was noted that, close to some domains, the ions extended their duration near the surface, suggesting that the local electrostatic potential prevented them from diffusing to the bulk. During the time frame in which the ions were detained next to the surface, they could rapidly shuttle between various attractor sites located under the electrostatic umbrella. Statistical analysis of molecular dynamics and electrostatic potential/entropy consideration indicated that the detainment state is an energetic compromise between attractive forces and entropy of dilution. The similarity between the motion of free ions next to a protein and the proton transfer on the protein's surface are discussed.
Journal of Chemical Theory and Computation, 2012
Implicit solvation is a mean force approach to model solvent forces acting on a solute molecule. It is frequently used in molecular simulations to reduce the computational cost of solvent treatment. In the first instance, the free energy of solvation and the associated solvent−solute forces can be approximated by a function of the solvent-accessible surface area (SASA) of the solute and differentiated by an atom−specific solvation parameter σ i SASA . A procedure for the determination of values for the σ i SASA parameters through matching of explicit and implicit solvation forces is proposed. Using the results of Molecular Dynamics simulations of 188 topologically diverse protein structures in water and in implicit solvent, values for the σ i SASA parameters for atom types i of the standard amino acids in the GROMOS force field have been determined. A simplified representation based on groups of atom types σ g SASA was obtained via partitioning of the atom−type σ i SASA distributions by dynamic programming. Three groups of atom types with well separated parameter ranges were obtained, and their performance in implicit versus explicit simulations was assessed. The solvent forces are available at http://mathbio.nimr.mrc.ac.uk/wiki/ Solvent_Forces.
A Heuristic Molecular Model of Hydrophobic Interactions
1995
Hydrophobic interactions provide driving forces for protein folding, membrane formation, and oil-water separation. Motivated by information theory, the poorly understood nonpolar solute interactions in water are investigated. A simple heuristic model of hydrophobic effects in terms of density fluctuations is developed. This model accounts quantitatively for the central hydrophobic phenomena of cavity formation and association of inert gas solutes; it therefore clarifies the underlying physics of hydrophobic effects and permits important applications to conformational equilibria of nonpolar solutes and hydrophobic residues in biopolymers.
Methods in molecular biology (Clifton, N.J.)
The effects of solvation on molecular recognition are investigated from different perspectives, ranging from methods to analyse explicit solvent dynamical behaviour at the protein surface to methods for the implicit treatment of solvent effects associated with the conformational behaviour of biomolecules. The here presented implicit solvation method is based on an analytical approximation of the Solvent Accessible Surface Area (SASA) of solute molecules, which is computationally efficient and easy to parametrise. The parametrised SASA solvation method is discussed in the light of protein design and ligand binding studies. The POPS program for the SASA computation on single molecules and complex interfaces is described in detail. Explicit solvent behaviour is described here in the form of solvent density maps at the protein surface. We highlight the usefulness of that approach in defining the organisation of specific water molecules at functional sites and in determining hydrophobicity scores for the identification of potential interaction patches.