Hydration Properties and Solvent Effects for All-Atom Solutes in Polarizable Coarse-Grained Water

Yan, Xin; Tirado‐Rives, Julian; Jorgensen, William L.

doi:10.1021/acs.jpcb.6b00399

Cited by 10 publications

(8 citation statements)

References 72 publications

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“…Omitting it reduces the MUE to 1.58 kcal/mol. Since it is known that nitrogen atoms in aromatic rings can be problematic for CM1A charges, 73 it was decided to test as well the original OPLS-AA force field charges of all ligands, which were parameterized by computing the structural and thermodynamic properties of pure organic liquids. 74 The results for the charge perturbation for indole (Supplementary Table S1) suggested that the molecule is too polar with the scaled CM1A charges.…”

Section: Resultsmentioning

confidence: 99%

Enhanced Monte Carlo Methods for Modeling Proteins Including Computation of Absolute Free Energies of Binding

Qian

Vilseck

Tirado‐Rives

et al. 2018

J. Chem. Theory Comput.

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The generation of a complete ensemble of geometrical configurations is required to obtain reliable estimations of absolute binding free energies by alchemical free energy methods. Molecular dynamics (MD) is the most popular sampling method, but the representation of large biomolecular systems may be incomplete owing to energetic barriers that impede efficient sampling of the configurational space. Monte Carlo (MC) methods can possibly overcome this issue by adapting the attempted movement sizes to facilitate transitions between alternative local-energy minima. In this study, we present an MC statistical mechanics algorithm to explore the protein-ligand conformational space with emphasis on the motions of the protein backbone and side chains. The parameters for each MC move type were optimized to better reproduce conformational distributions of 18 dipeptides and the well-studied T4-lysozyme L99A protein. Next, the performance of the improved MC algorithms was evaluated by computing absolute free energies of binding for L99A lysozyme with benzene and seven analogs. Results for benzene with L99A lysozyme from MD and the optimized MC protocol were found to agree within 0.6 kcal/mol, while a mean unsigned error of 1.2 kcal/mol between MC results and experiment was obtained for the seven benzene analogs. Significant advantages in computation speed are also reported with MC over MD for similar extents of configurational sampling.

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Section: Resultsmentioning

confidence: 99%

Enhanced Monte Carlo Methods for Modeling Proteins Including Computation of Absolute Free Energies of Binding

Qian

Vilseck

Tirado‐Rives

et al. 2018

J. Chem. Theory Comput.

Self Cite

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“…In single-layer schemes, the solvent is described at a unique CG level (figure 1a). Although different schemes for direct coupling of a FG solute with a CG solvent have been proposed, reproduction of relative stability of peptide conformations and hydrogen bond patterns has posed special difficulties to this multi-scale solvation approach [19][20][21]. However, two methods worth highlighting use simple Lennard-Jones (LJ) water models [17] or the ELBA CG solvent [22,23].…”

Section: Fixed Resolutions Single-layer Solvationmentioning

confidence: 99%

From quantum to subcellular scales: multi-scale simulation approaches and the SIRAH force field

et al. 2019

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Modern molecular and cellular biology profits from astonishing resolution structural methods, currently even reaching the whole cell level. This is encompassed by the development of computational methods providing a deep view into the structure and dynamics of molecular processes happening at very different scales in time and space. Linking such scales is of paramount importance when aiming at far-reaching biological questions. Computational methods at the interface between classical and coarse-grained resolutions are gaining momentum with several research groups dedicating important efforts to their development and tuning. An overview of such methods is addressed herein, with special emphasis on the SIRAH force field for coarse-grained and multi-scale simulations. Moreover, we provide proof of concept calculations on the implementation of a multi-scale simulation scheme including quantum calculations on a classical fine-grained/coarse-grained representation of double-stranded DNA. This opens the possibility to include the effect of large conformational fluctuations in chromatin segments on, for instance, the reactivity of particular base pairs within the same simulation framework.

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“…An alternative approach to implicit solvent models is to treat the solvent explicitly but at a coarser level of resolution, i.e., hybrid QM/MM approaches, ,− or atomistic/coarse-grained (AT/CG) simulations. − In a CG representation, multiple atoms are combined into a larger bead that consists of one or more particles (for reviews see, e.g., refs − ). For solvents, so-called supramolecular CG models have also been developed where several molecules are represented by a single CG bead. , The description of the interface between the levels of resolution is key in hybrid simulations.…”

Section: Introductionmentioning

confidence: 99%

“…For solvents, so-called supramolecular CG models have also been developed where several molecules are represented by a single CG bead. , The description of the interface between the levels of resolution is key in hybrid simulations. In AT/CG approaches, the AT-CG interactions are either completely reparametrized , or based on standard combination rules − ,− with additional scaling in some cases, as for example in ref .…”

Section: Introductionmentioning

confidence: 99%

Benchmarking Hybrid Atomistic/Coarse-Grained Schemes for Proteins with an Atomistic Water Layer

Renevey

Riniker

2019

J. Phys. Chem. B

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An approach to overcome the limited time and spatial scales in molecular dynamics (MD) simulations is to reduce the number of degrees of freedom in the system through coarse-graining. In hybrid atomistic/coarse-grained (AT/CG) simulations, the region of interest (e.g., the solute) is simulated at a higher level of resolution than the surrounding solvent. Recently, we have reparametrized the interactions between the GROMOS 54A7 force field and the GROMOS CG water model to correctly reproduce solvation free energies of side-chain analogues. In this study, a benchmarking of the AT-CG parametrization using a broad set of 22 proteins is conducted. On the basis of the results, the idea of introducing a thin AT water layer around the solute (protein) is revisited to provide a detailed first solvation shell. Different layer schemes were investigated: (a) the water molecules in the AT water layer around the whole protein were restrained to their respective closest protein atom, and (b) the AT water layer was present only around the charged side chains. Results show that the second scheme is more robust in practice and reduces artifacts from the hybrid model with only a small additional computational cost. In general, this layer scheme was found to preserve the structural properties of the proteins better compared to direct solvation in CG water.

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Hydration Properties and Solvent Effects for All-Atom Solutes in Polarizable Coarse-Grained Water

Cited by 10 publications

References 72 publications

Enhanced Monte Carlo Methods for Modeling Proteins Including Computation of Absolute Free Energies of Binding

Enhanced Monte Carlo Methods for Modeling Proteins Including Computation of Absolute Free Energies of Binding

From quantum to subcellular scales: multi-scale simulation approaches and the SIRAH force field

Benchmarking Hybrid Atomistic/Coarse-Grained Schemes for Proteins with an Atomistic Water Layer

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