“Martinizing” the Variational Implicit Solvent Method (VISM): Solvation Free Energy for Coarse-Grained Proteins

Ricci, Clarisse Gravina; Li, Bo; Cheng, Li-Tien; Dzubiella, Joachim; McCammon, J. Andrew

doi:10.1021/acs.jpcb.7b04113

Cited by 12 publications

(14 citation statements)

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“…It uses an effective solvation free-energy function that depends solely on the position of solute-solvent interface and solute atoms. It couples several energy terms such as the volume and interface energies of solutes, the solute-solvent VDW interaction energy and the solute-solute mechanical interactions energy (Zhou et al, 2014 ; Sun et al, 2015 ; Ricci et al, 2017 ). In addition, a curvature dependent surface tension is incorporated to account for the different hydration of concave and convex surfaces.…”

mentioning

confidence: 99%

Gaussian-Based Smooth Dielectric Function: A Surface-Free Approach for Modeling Macromolecular Binding in Solvents

Chakravorty

Jia

Peng

et al. 2018

Front. Mol. Biosci.

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Conventional modeling techniques to model macromolecular solvation and its effect on binding in the framework of Poisson-Boltzmann based implicit solvent models make use of a geometrically defined surface to depict the separation of macromolecular interior (low dielectric constant) from the solvent phase (high dielectric constant). Though this simplification saves time and computational resources without significantly compromising the accuracy of free energy calculations, it bypasses some of the key physio-chemical properties of the solute-solvent interface, e.g., the altered flexibility of water molecules and that of side chains at the interface, which results in dielectric properties different from both bulk water and macromolecular interior, respectively. Here we present a Gaussian-based smooth dielectric model, an inhomogeneous dielectric distribution model that mimics the effect of macromolecular flexibility and captures the altered properties of surface bound water molecules. Thus, the model delivers a smooth transition of dielectric properties from the macromolecular interior to the solvent phase, eliminating any unphysical surface separating the two phases. Using various examples of macromolecular binding, we demonstrate its utility and illustrate the comparison with the conventional 2-dielectric model. We also showcase some additional abilities of this model, viz. to account for the effect of electrolytes in the solution and to render the distribution profile of water across a lipid membrane.

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confidence: 99%

Gaussian-Based Smooth Dielectric Function: A Surface-Free Approach for Modeling Macromolecular Binding in Solvents

Chakravorty

Jia

Peng

et al. 2018

Front. Mol. Biosci.

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“…Still towards a much better scaling of the classical approaches for the dynamic simulation of systems of very large dimensions, it is worth recalling here the important progress seen in the last years in the accuracy and robustness of coarse grained (CG) force fields 137,138 that can now also include polarization effects. Examples of integration among different classical models (from atomistic to CG and continuum) have already been proposed in the literature 139,140 but this integration still needs to be enhanced to describe composite systems combing biomacromolecules, complex biological environments such as membranes and nonbiological nanostructures. Another necessary direction to explore, is the introduction of possible "chemical" interactions between the target and the environment.…”

Section: Discussionmentioning

confidence: 99%

Multiscale modelling of photoinduced processes in composite systems

2019

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| In the last decades, the quantum mechanical modeling has moved from isolated molecules made of few atoms, to large supramolecular aggregates embedded in complex environments. This has been made possible by the important progress achieved by multiscale models based on the integration of QM methods with classical descriptions. One of the first example of this integration is represented by continuum solvation models that starting from the eighties of the last century have been largely and successfully applied to predict properties and processes of solvated molecules. Almost in the same years, another alternative classical description, based on Molecular Mechanics (MM) has been coupled to QM methods to give the hybrid QM/MM approach. Since their first formulations, these QM/classical models have seen an enormous development in terms of accuracy, robustness and generalizability. This progress has allowed their application to systems of increasing complexity and to processes never faced before within a QM framework. An important example of such an achievement is represented by the novel insights reached in the fundamental understanding and the possible exploitation of photoinduced processes in biomolecules, nanomaterials and, more in general, composite systems where different "objects" of molecular, nano and mesoscopic scale are coupled together. In this review, we highlight the potentials and the limitations of such modeling, thereby showing which developments are still needed to definitely make the QM-based multiscale strategy the gold-standard for explaining the outputs of novel advanced spectroscopic techniques and predicting the outcome of light-activated events in composite systems. The multiscale strategiesIn the years, two main strategies to combine QM descriptions of the target and classical models of the environment, have been proposed. Interestingly, their first formulations date back to the same years, namely the end of the seventies of the previous century. [8][9][10] The two strategies refer to continuum and discrete (or atomistic) descriptions of the environment, respectively. In the latter case, the atoms of the environment (or group of atoms in coarser grained versions of the model) are treated through a Molecular Mechanics (MM) force field (FF). [11][12][13][14][15] In the former case, instead, the atomic nature of the environment is lost and a continuum description in terms of macroscopic properties is introduced instead. 16-18 Despite this huge "modellistic" difference, the two formulations present important common elements when reconsidered from the point of view of the QM target. In any case, for simplicity's sake two separate presentations will be given. QM/continuum. If the environment loses its atomic nature, an effective description has to be introduced which is based on some macroscopic properties. This is exactly what is done in continuum models where the target sees the environment as an infinite dielectric medium characterized by a (generally) frequency and position dependent permittivit...

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“…Application of this new method, denominated M VISM, to estimate the solvation free energies of six different proteins revealed a good qualitative agreement between the fully coarse-grained approach and the atomistic version obtained with the original LS-VISM. We also found the solvation free energies obtained with M VISM to be significantly underestimated due to un-optimized (too favorable) Lennard-Jones interaction energies between solute and water (Ricci et al, 2017 ). Overestimation of van der Waals interactions is characteristic of MARTINI, as reported in hydration of organic compounds (Marrink et al, 2007 ), protein-protein binding (Stark et al, 2013 ) and aggregation of polysaccharides (Schmalhorst et al, 2017 ).…”

Section: Ls-vism Applications To Molecular Association and Bindingmentioning

confidence: 96%

“…Combining VISM with a coarse-grained model for the solute is an interesting step to push VISM toward large-scale applications and eventually merge it with molecular dynamics simulations. Recently, we adapted VISM to produce solvation free energies for “martinized” proteins (Ricci et al, 2017 ). The MARTINI model is a well-established meso-scale force field for modeling large molecular systems, which replaces groups of atoms by interaction centers commonly referred to as “beads,” based on an approximate 4-to-1 mapping (Marrink et al, 2004 , 2007 ; Monticelli et al, 2008 ).…”

Section: Ls-vism Applications To Molecular Association and Bindingmentioning

confidence: 99%

“…In fact, increasing the strength of LJ interactions is a way of compensating for (i) the simplistic treatment given to electrostatic interactions in the Martini model, and (ii) the reduced number of degrees of freedom in Martini water, which can significantly reduce entropically-driven hydrophobic attraction between apolar molecules. In M VISM, overestimation of van der Waals interactions could be easily fixed by a simple downscaling of the Martini ε i values, which brought solvation energies from the fully coarse-grained approach to fairly good quantitative agreement with the ones from the atomistic approach, while also providing a better partition of the solvation free energy among the coupled energy terms (hydrophobic, Lennard-Jones, and electrostatics) (Ricci et al, 2017 ).…”

Section: Ls-vism Applications To Molecular Association and Bindingmentioning

confidence: 99%

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Tailoring the Variational Implicit Solvent Method for New Challenges: Biomolecular Recognition and Assembly

Ricci

Cheng

et al. 2018

Front. Mol. Biosci.

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Predicting solvation free energies and describing the complex water behavior that plays an important role in essentially all biological processes is a major challenge from the computational standpoint. While an atomistic, explicit description of the solvent can turn out to be too expensive in large biomolecular systems, most implicit solvent methods fail to capture “dewetting” effects and heterogeneous hydration by relying on a pre-established (i.e., guessed) solvation interface. Here we focus on the Variational Implicit Solvent Method, an implicit solvent method that adds water “plasticity” back to the picture by formulating the solvation free energy as a functional of all possible solvation interfaces. We survey VISM's applications to the problem of molecular recognition and report some of the most recent efforts to tailor VISM for more challenging scenarios, with the ultimate goal of including thermal fluctuations into the framework. The advances reported herein pave the way to make VISM a uniquely successful approach to characterize complex solvation properties in the recognition and binding of large-scale biomolecular complexes.

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“Martinizing” the Variational Implicit Solvent Method (VISM): Solvation Free Energy for Coarse-Grained Proteins

Cited by 12 publications

References 51 publications

Gaussian-Based Smooth Dielectric Function: A Surface-Free Approach for Modeling Macromolecular Binding in Solvents

Gaussian-Based Smooth Dielectric Function: A Surface-Free Approach for Modeling Macromolecular Binding in Solvents

Multiscale modelling of photoinduced processes in composite systems

Tailoring the Variational Implicit Solvent Method for New Challenges: Biomolecular Recognition and Assembly

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