An efficient hybrid explicit/implicit solvent method for biomolecular simulations

Lee, Michael S.; Salsbury, Freddie R.; Olson, Mark A.

doi:10.1002/jcc.20119

Cited by 119 publications

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References 53 publications

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“…Toward this goal, various improvements of implicit models have been introduced (21, 22), explicit solvents have been coarse-grained (23, 24), and hybrid explicit-implicit models have been developed (25)(26)(27)(28)(29). Here, we take a different approach.…”

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Modeling aqueous solvation with semi-explicit assembly

Fennell¹,

Kehoe

Dill³

2011

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

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We describe a computational solvation model called semi-explicit assembly (SEA). SEA water captures much of the physics of explicitsolvent models but with computational speeds approaching those of implicit-solvent models. We use an explicit-water model to precompute properties of water solvation shells around simple spheres, then assemble a solute's solvation shell by combining the shells of these spheres. SEA improves upon implicit-solvent models of solvation free energies by accounting for local solute curvature, accounting for near-neighbor nonadditivities, and treating water's dipole as being asymmetrical with respect to positive or negative solute charges. SEA does not involve parameter fitting, because parameters come from the given underlying explicitsolvation model. SEA is about as accurate as explicit simulations as shown by comparisons against four different homologous alkyl series, a set of 504 varied solutes, solutes taken retrospectively from two solvation-prediction events, and a hypothetical polarsolute series, and SEA is about 100-fold faster than Poisson-Boltzmann calculations.free energy | implicit solvent | transfer W e describe here an approach for computing the free energies of solvation of solutes in water. Aqueous solvation has been modeled at different levels, ranging from detailed quantum mechanics simulations of few-molecule clusters (1, 2), to faster classical simulations using up to tens of thousands of explicit molecules (3-10), to very fast models in which water is treated implicitly as a simple uniform continuous medium (11)(12)(13)(14)(15)(16)(17). For large computations, such as those in typical biomolecule simulations, explicit-water modeling can be slow and expensive, so it is common to use implicit water instead. However, implicit models often require trade-offs in the physics that can limit their accuracies. For example, water is typically treated as a continuum rather than individual particles, and this neglects discrete microscopic effects; nonpolar solvation effects are often assumed to depend only on surface area A (expressed as γA), and not on detailed dispersive interactions and collective consequences of solute shape (18)(19)(20).It would be useful to have a computational model of water that is both fast-approaching the speeds of the fastest implicitsolvent models-and that captures the physics and the transferability of explicit-solvent models. Toward this goal, various improvements of implicit models have been introduced (21, 22), explicit solvents have been coarse-grained (23, 24), and hybrid explicit-implicit models have been developed (25)(26)(27)(28)(29). Here, we take a different approach. We precompute solvation properties of water in explicit-solvent simulations of simple spheres, which we then apply in summations over assemblies about arbitrary solutes. As the details of the solvation response come entirely from the physics of an explicit solvent, this model lacks free parameters from statistical fits to solute molecular transfer free energies, resulting in a ...

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confidence: 99%

Modeling aqueous solvation with semi-explicit assembly

Fennell¹,

Kehoe

Dill³

2011

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

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“…Outside the cavity, on the other hand, by assuming that the mobile ion concentration follows the DebyeHückel theory, the electric field Ψ out (r) is then given by the solution of the linearized PoissonBoltzmann equation (LPBE) (1) where λ is the inverse Debye screening length which is proportional to the square root of the ionic concentration c s measured in molar units [4] (λ = 0 for the pure water solvent). On the interface Γ of the dielectric prolate spheroid and its surrounding dielectric medium, the continuity of the tangential component of the electric field and the normal component of the displacement field requires that (2) where n is the outward normal of the interface Γ.…”

Section: A General Electrostatic Problemmentioning

confidence: 99%

“…Since this is a basic electrostatic problem, and most importantly, since it has potential applications in hybrid explicit/implicit solvation simulations [1][2][3] for biomacromolecules of irregular shapes, the exact solution should be made known. It should be mentioned, however, that the exact solution to a similar electrostatic problem in which the point charge is set outside a dielectric or conducting prolate spheroid can be found in [9][10][11].…”

Section: A Prolate Spheroid Immersed In the Pure Water Solventmentioning

confidence: 99%

“…(37) where and As stated in Section 1, the more general problem in which the dielectric cavity contains a finite number of point charges can be solved by means of linear superposition. More precisely, let a total of L point charges q 1 , q 2 ,…, q L be located at L arbitrary points r l = (ξ l , η l , ϕ l ), l = 1, 2,…, L inside the prolate spheroid, although in hybrid explicit/implicit solvent biomolecular simulations [1][2][3], these point charges are in general uniformly distributed in the dielectric cavity. Then at a point r = (ξ, η, ϕ) outside the spheroid the potential takes on the form (42) and correspondingly at a point inside the spheroid it takes on the form (43) where for each point charge q l , the associated expansion coefficients and are determined by the system in Eqs.…”

Section: Numerical Approximationmentioning

confidence: 99%

“…The electric field inside the cavity is thus expressed asΨ in = Ψ s + Ψ RF , where Ψ s is the Coulomb potential which can be simply calculated by the well-known Coulomb's Law, and Ψ RF is the reaction field which will dominate the computational cost for calculating the electric field inside the cavity. Such a problem could be encountered in many applications such as hybrid explicit/ implicit solvent biomolecular dynamics simulations [1][2][3]. In particular, in this note we are interested in the exact solution of the problem when the dielectric cavity is either a sphere or a prolate spheroid, and the surrounding medium is either the pure water solvent or an ionic solvent of low ionic strength.…”

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Electrostatic potential of point charges inside dielectric prolate spheroids

Deng¹

2008

Journal of Electrostatics

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The exact solution to an electrostatic problem of finding the electric potential of point charges inside a dielectric prolate spheroid is discussed in this note by using the classical electrostatic theory, where the prolate spheroid is embedded in a dissimilar dielectric medium. Such a problem may find its application in hybrid solvent biomolecular simulations, in which biomolecules and a part of solvent molecules within a dielectric cavity are explicitly modeled while a surrounding dielectric continuum is used to model bulk effects of the solvent beyond the cavity. Numerical experiments have demonstrated the convergence of the proposed series solutions. Keywords A general electrostatic problemA finite number of point charges are set inside a dielectric cavity of electric permittivity ε i , which is embedded in a homogeneous, isotropic dielectric medium of electric permittivity ε o . The point charges will polarize the surrounding dielectric medium, which in turn makes a contribution, called the reaction field, to the electric field throughout the cavity. The electric field inside the cavity is thus expressed asΨ in = Ψ s + Ψ RF , where Ψ s is the Coulomb potential which can be simply calculated by the well-known Coulomb's Law, and Ψ RF is the reaction field which will dominate the computational cost for calculating the electric field inside the cavity. Such a problem could be encountered in many applications such as hybrid explicit/ implicit solvent biomolecular dynamics simulations [1][2][3]. In particular, in this note we are interested in the exact solution of the problem when the dielectric cavity is either a sphere or a prolate spheroid, and the surrounding medium is either the pure water solvent or an ionic solvent of low ionic strength.By the principle of linear superposition, the electrostatic problem with a single source charge q inside a dielectric cavity only needs to be considered. It is then well-known that the total electric potential Ψ in (r) inside the cavity is given by the solution of the Poisson equation *Tel

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Molecular Modeling of Nucleic Acid Structure: Electrostatics and Solvation

Bergonzo

Galindo‐Murillo

Cheatham

2013

CP Nucleic Acid Chemistry

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This unit presents an overview of computer simulation techniques as applied to nucleic acid systems, ranging from simple in vacuo molecular modeling techniques to more complete all-atom molecular dynamics treatments that include an explicit representation of the environment. The third in a series of four units, this unit focuses on critical issues in solvation and the treatment of electrostatics. UNITS 7.5 & 7.8 introduced the modeling of nucleic acid structure at the molecular level. This included a discussion of how to generate an initial model, how to evaluate the utility or reliability of a given model, and ultimately how to manipulate this model to better understand the structure, dynamics, and interactions. Subject to an appropriate representation of the energy, such as a specifically parameterized empirical force field, the techniques of minimization and Monte Carlo simulation, as well as molecular dynamics (MD) methods, were introduced as means to sample conformational space for a better understanding of the relevance of a given model. From this discussion, the major limitations with modeling, in general, were highlighted. These are the difficult issues in sampling conformational space effectively-the multiple minima or conformational sampling problems-and accurately representing the underlying energy of interaction. In order to provide a realistic model of the underlying energetics for nucleic acids in their native environments, it is crucial to include some representation of solvation (by water) and also to properly treat the electrostatic interactions. These are discussed in detail in this unit. SubjectNucleic Acid Chemistry; Nucleic Acid Structure and Folding; Structural Analysis of Biomolecules; Experimental Determination of Structure ELECTROSTATICS AND SOLVATIONAccurately modeling the structure and dynamics of nucleic acids with standard ab initio or empirical potentials presents special difficulties due to the highly charged phosphate backbone and the observation that nucleic acids are essentially always hydrated. Even under extremely dehydrating conditions, DNA still has very tightly associated water. To apply an accurate model, some representation of this structural and solvating water is likely necessary. Water has a structural role as both a donor and acceptor of hydrogen bonds, and Internet ResourcesAscona B-DNA Consortium website.

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An efficient hybrid explicit/implicit solvent method for biomolecular simulations

Cited by 119 publications

References 53 publications

Modeling aqueous solvation with semi-explicit assembly

Modeling aqueous solvation with semi-explicit assembly

Electrostatic potential of point charges inside dielectric prolate spheroids

Molecular Modeling of Nucleic Acid Structure: Electrostatics and Solvation

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