Determining thermodynamic properties of molecular interactions from single crystal studies

Zanden, Crystal M. Vander; Carter, Megan; Ho, P Shing

doi:10.1016/j.ymeth.2013.07.039

Cited by 15 publications

(25 citation statements)

References 23 publications

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“…By determining the ratio of Br at the crossing and noncrossing strands in the single-crystal structure, the Br XB energy was estimated to be $ 17 kJ mol À1 more stabilizing than the competing HB in this DNA system. The work of Carter et al (2013) extended this crystallographic assay to F, Cl and I, and applied differential scanning calorimetry (DSC) to determine the explicit stabilizing potentials in solution (Vander Zanden et al, 2013). From the crystallographic studies, the ability of XBs to effectively compete against the HB followed the expected series F < Cl < Br I.…”

Section: Competitive Relationships: Hb Against Xbmentioning

confidence: 99%

Relationships between hydrogen bonds and halogen bonds in biological systems

Rowe

2017

Acta Crystallogr Sect B

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The recent recognition that halogen bonding (XB) plays important roles in the recognition and assembly of biological molecules has led to new approaches in medicinal chemistry and biomolecular engineering. When designing XBs into strategies for rational drug design or into a biomolecule to affect its structure and function, we must consider the relationship between this interaction and the more ubiquitous hydrogen bond (HB). In this review, we explore these relationships by asking whether and how XBs can replace, compete against or behave independently of HBs in various biological systems. The complex relationships between the two interactions inform us of the challenges we face in fully utilizing XBs to control the affinity and recognition of inhibitors against their therapeutic targets, and to control the structure and function of proteins, nucleic acids and other biomolecular scaffolds.

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Section: Competitive Relationships: Hb Against Xbmentioning

confidence: 99%

Relationships between hydrogen bonds and halogen bonds in biological systems

Rowe

2017

Acta Crystallogr Sect B

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“…The system competes a BXB against analogous H-bonds to stabilize a four-stranded DNA junction 15 and, with the energy of the H-bond now determined, the actual energy of each BXB geometry can be determined in isolation 17, 40 . Using this system, we have shown that the strength of halogen bonds increases according to the series F < Cl < Br < I, with energies ranging from −0.52 to −6 kcal/mol 17 .…”

Section: Introductionmentioning

confidence: 99%

Force Field Model of Periodic Trends in Biomolecular Halogen Bonds

et al. 2014

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The study of the noncovalent interaction now defined as a halogen bond (X-bond) has become one of the fastest growing areas in experimental and theoretical chemistry—its applications as a design tool are highly extensive. The significance of the interaction in biology has only recently been recognized, but has now become important in medicinal chemistry. We had previously derived a set of empirical potential energy functions to model the structure-energy relationships for bromines in biomolecular X-bonds (BXBs). Here, we have extended this force field for BXBs (ffBXB) to the halogens (Cl, Br, and I) that are commonly seen to form stable X-bonds. The ffBXB calculated energies show a remarkable one-to-one linear relationship to explicit BXB energies determined from an experimental DNA junction system, thereby validating the approach and the model. The resulting parameters allow us to interpret the stabilizing effects of BXBs in terms of well-defined physical properties of the halogen atoms, including their size, shape, and charge, showing periodic trends that are predictable along the Group VII column of elements. Consequently, we have established the ffBXB as accurate computational tool that can be applied to, for example, for the design of new therapeutic compounds against clinically important targets and new biomolecular based materials.

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“…The XB can be further tuned according to the electron withdrawing ability of the compound to which the halogen is covalently bonded, , with aromatic groups accentuating XBs . XB energies to anionic oxygen acceptors measured in a model DNA system are equal to or greater than that of a competing HB. − Furthermore, their geometries become more ideal (with shorter distances and more linear alignment to the XC bond, Θ XB ) as their strength increases . The structure–energy relationships of XBs to a neutral carbonyl oxygen acceptor in a protein, ,− however, have not been previously determined.…”

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confidence: 99%

Structure–Energy Relationships of Halogen Bonds in Proteins

et al. 2017

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The structures and stabilities of proteins are defined by a series of weak noncovalent electrostatic, van der Waals, and hydrogen bond (HB) interactions. In this study, we have designed and engineered halogen bonds (XBs) site-specifically to study their structure-energy relationship in a model protein, T4 lysozyme. The evidence for XBs is the displacement of the aromatic side chain toward an oxygen acceptor, at distances that are equal to or less than the sums of their respective van der Waals radii, when the hydroxyl substituent of the wild-type tyrosine is replaced by a halogen. In addition, thermal melting studies show that the iodine XB rescues the stabilization energy from an otherwise destabilizing substitution (at an equivalent noninteracting site), indicating that the interaction is also present in solution. Quantum chemical calculations show that the XB complements an HB at this site and that solvent structure must also be considered in trying to design molecular interactions such as XBs into biological systems. A bromine substitution also shows displacement of the side chain, but the distances and geometries do not indicate formation of an XB. Thus, we have dissected the contributions from various noncovalent interactions of halogens introduced into proteins, to drive the application of XBs, particularly in biomolecular design.

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Determining thermodynamic properties of molecular interactions from single crystal studies

Cited by 15 publications

References 23 publications

Relationships between hydrogen bonds and halogen bonds in biological systems

Relationships between hydrogen bonds and halogen bonds in biological systems

Force Field Model of Periodic Trends in Biomolecular Halogen Bonds

Structure–Energy Relationships of Halogen Bonds in Proteins

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