A revised potential-energy surface for molecular mechanics studies of carbohydrates

Ha, Sookhee; Giammona, Ann; Field, Martin J.; Brady, John W.

doi:10.1016/0008-6215(88)80078-8

Cited by 287 publications

(178 citation statements)

References 38 publications

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“…Brady and coworkers have developed models for hexopyranose sugars based on small molecule geometric and vibrational data and on ␣-D-glucopyranose. 289 However, this force field yields incorrect conformational properties for the exocyclic hydroxyl, 290 glycosyl bonds are not treated, and the model is only limited to hydroxyl substituents. More recently, this model has been reoptimized, in part to be consistent with the CHARMM22 protein and CHARMM27 nucleic acid/lipid force fields and to yield improved conformational properties for the exocyclic hydroxyl group.…”

Section: Carbohydratesmentioning

confidence: 99%

Empirical force fields for biological macromolecules: Overview and issues

2004

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Empirical force field-based studies of biological macromolecules are becoming a common tool for investigating their structure-activity relationships at an atomic level of detail. Such studies facilitate interpretation of experimental data and allow for information not readily accessible to experimental methods to be obtained. A large part of the success of empirical force field-based methods is the quality of the force fields combined with the algorithmic advances that allow for more accurate reproduction of experimental observables. Presented is an overview of the issues associated with the development and application of empirical force fields to biomolecular systems. This is followed by a summary of the force fields commonly applied to the different classes of biomolecules; proteins, nucleic acids, lipids, and carbohydrates. In addition, issues associated with computational studies on "heterogeneous" biomolecular systems and the transferability of force fields to a wide range of organic molecules of pharmacological interest are discussed.

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Section: Carbohydratesmentioning

confidence: 99%

Empirical force fields for biological macromolecules: Overview and issues

2004

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“…The CHARMM force-field was used for the protein, and the TIP3P model [32] was used for water. A force-field was constructed for glycerol using the standard CHARMM geometries and partial charges for the atoms in a -CHOH-unit [26], [27]. Urea was assumed to be planar with bond lengths equal to the CHARMM standards and partial charges recomputed as done previously [33] but using the CHARMM van der Waals mixing rules in the objective function.…”

Section: A Molecular Simulationsmentioning

confidence: 99%

Proteins in Mixed Solvents: A Molecular-Level Perspective

2003

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Abstract-We present a statistical mechanical approach for quantifying thermodynamic properties of proteins in mixed solvents. This approach, based on molecular dynamics simulations which incorporate all atom models and the theory of preferential binding, allows us to compute transfer free energies with experimental accuracy and does not incorporate any adjustable parameters. Specifically, we applied our approach to the model proteins RNase A and T1, and the solvent components water, glycerol, and urea. We found that the observed differences in the binding of glycerol and urea to RNase T1 and A are predominantly a consequence of density differences in the first coordination shell of the protein with the cosolvents, but the second solvation shell also contributes to the overall binding coefficients. The success of this approach in modeling preferential binding indicates that it incorporates the important underlying physics of proteins in mixed solvent systems and that the difficulty in quantitative prediction to date can be surmounted by explicitly incorporating the complex protein-solvent and solvent-solvent interactions.

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“…We can estimate the order of magnitude of the enthalpic elasticity of a stretched boat conformer by considering the bending energy term in the CHARMM force-field parameterization of the glucopyranose ring. Ha et al (1988) provided k Ϸ90 kcal͞(mol rad 2 ) for the bending of a COOEOC bond (32), where OE is the ring oxygen. This is equivalent to an enthalpic elasticity of Ϸ60,000 pN͞nm.…”

Section: Two-state Model Fits the Data In The Vicinity Of The Conformmentioning

confidence: 99%

Chair-boat transitions in single polysaccharide molecules observed with force-ramp AFM

Marszałek

Oberhauser

et al. 2002

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

136

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Under a stretching force, the sugar ring of polysaccharide molecules switches from the chair to the boat-like or inverted chair conformation. This conformational change can be observed by stretching single polysaccharide molecules with an atomic force microscope. In those early experiments, the molecules were stretched at a constant rate while the resulting force changed over wide ranges. However, because the rings undergo force-dependent transitions, an experimental arrangement where the force is the free variable introduces an undesirable level of complexity in the results. Here we demonstrate the use of force-ramp atomic force microscopy to capture the conformational changes in single polysaccharide molecules. Force-ramp atomic force microscopy readily captures the ring transitions under conditions where the entropic elasticity of the molecule is separated from its conformational transitions, enabling a quantitative analysis of the data with a simple two-state model. This analysis directly provides the physico-chemical characteristics of the ring transitions such as the width of the energy barrier, the relative energy of the conformers, and their enthalpic elasticity. Our experiments enhance the ability of single-molecule force spectroscopy to make high-resolution measurements of the conformations of single polysaccharide molecules under a stretching force, making an important addition to polysaccharide spectroscopy. S ingle molecule force spectroscopy has become an important tool to examine the conformations of proteins and polysaccharide molecules under a stretching force (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Recent experiments have demonstrated that a force field can trigger conformational changes in these molecules that cannot be observed by traditional NMR or x-ray crystallographic techniques. Force spectroscopy involves measuring the force required to extend a molecule by a certain amount (2-10). The data are compiled into a forceextension relationship that gives a characteristic fingerprint for the conformational transitions of the molecule under study. For example, force-extension relationships of polysaccharides such as amylose and dextran (13, 14) display a characteristic plateau (2, 4) that marks forced transitions of the glucose monomers from their chair conformation to the boat-like conformation (4). Similarly, two distinct plateaus in the force-extension curve of pectin (13, 14) report a transition of the galactose rings from the chair conformation to the boat conformation and a subsequent flip of the boat to the inverted chair conformation (5). These observations provide an interesting perspective on the behavior of polysaccharides under mechanical tension (15) and suggest that fingerprints of forced conformational transitions can be used as a means for identifying single polysaccharides molecules in solution (9).In the most typical atomic force microscopy (AFM) experiment, a single molecule adsorbed between a substrate and the cantilever tip is extended vertically at a constant rate while t...

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A revised potential-energy surface for molecular mechanics studies of carbohydrates

Cited by 287 publications

References 38 publications

Empirical force fields for biological macromolecules: Overview and issues

Empirical force fields for biological macromolecules: Overview and issues

Proteins in Mixed Solvents: A Molecular-Level Perspective

Chair-boat transitions in single polysaccharide molecules observed with force-ramp AFM

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