Fast Calculation of van der Waals Volume as a Sum of Atomic and Bond Contributions and Its Application to Drug Compounds

Zhao, Yuan H.; Abraham, Michael H.; Zissimos, Andreas M.

doi:10.1021/jo034808o

Cited by 603 publications

(498 citation statements)

References 21 publications

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“…The solvent cavity at the base of the channel has a volume of ϳ315 Å 3 , as calculated from the molecular surface area of the cavity, and the van der Waals volume of HB is ϳ100 Å 3 (44). This accommodation within the active site is essential because we expect the HB moiety of HB-CoA to adopt different binding modes for initiation and elongation to establish the appropriate geometry for catalysis in each case.…”

Section: Structure Of the Cnphac Catalytic Domainmentioning

confidence: 99%

Structure of the Catalytic Domain of the Class I Polyhydroxybutyrate Synthase from Cupriavidus necator

Wittenborn¹,

Jost²,

Wei³

et al. 2016

Journal of Biological Chemistry

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Edited by F. Peter GuengerichPolyhydroxybutyrate synthase (PhaC) catalyzes the polymerization of 3-(R)-hydroxybutyryl-coenzyme A as a means of carbon storage in many bacteria. The resulting polymers can be used to make biodegradable materials with properties similar to those of thermoplastics and are an environmentally friendly alternative to traditional petroleum-based plastics. A full biochemical and mechanistic understanding of this process has been hindered in part by a lack of structural information on PhaC. Here we present the first structure of the catalytic domain (residues 201-589) of the class I PhaC from Cupriavidus necator (formerly Ralstonia eutropha) to 1.80 Å resolution. We observe a symmetrical dimeric architecture in which the active site of each monomer is separated from the other by ϳ33 Å across an extensive dimer interface, suggesting a mechanism in which polyhydroxybutyrate biosynthesis occurs at a single active site. The structure additionally highlights key side chain interactions within the active site that play likely roles in facilitating catalysis, leading to the proposal of a modified mechanistic scheme involving two distinct roles for the active site histidine. We also identify putative substrate entrance and product egress routes within the enzyme, which are discussed in the context of previously reported biochemical observations. Our structure lays a foundation for further biochemical and structural characterization of PhaC, which could assist in engineering efforts for the production of eco-friendly materials.

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Section: Structure Of the Cnphac Catalytic Domainmentioning

confidence: 99%

Structure of the Catalytic Domain of the Class I Polyhydroxybutyrate Synthase from Cupriavidus necator

Wittenborn¹,

Jost²,

Wei³

et al. 2016

Journal of Biological Chemistry

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“…The estimated average volumes of individual O h -and T d -symmetry cavities are 28,900 and 5,600 Å 3 , respectively. Given the 223 Å 3 van der Waal's volume 30 of BPA, and 55% by-volume occupancy 31 , the O h -and T d -symmetry cavities should be capable of hosting 71 and 14 molecules, respectively, of this hydrophobic guest. This general situation is illustrated for an O h -symmetry cavity in Fig.…”

Section: A Percolated Network Of Hydrophobic Holesmentioning

confidence: 99%

Host–guest chemistry with water-soluble gold nanoparticle supraspheres

et al. 2016

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The uptake of molecular guests, a hallmark of the supramolecular chemistry of cages and containers, has yet to be documented for soluble assemblies of metal nanoparticles. Here we demonstrate that gold nanoparticle-based supraspheres serve as a host for the hydrophobic uptake, transport and subsequent release of over two million organic guests, exceeding by five orders of magnitude the capacities of individual supramolecular cages or containers and rivalling those of zeolites and metal-organic frameworks on a mass-per-volume basis. The supraspheres are prepared in water by adding hexanethiol to polyoxometalate-protected 4 nm gold nanoparticles. Each 200 nm assembly contains hydrophobic cavities between the estimated 27,400 gold building blocks that are connected to one another by nanometre-sized pores. This gives a percolated network that effectively absorbs large numbers of molecules from water, including 600,000, 2,100,000 and 2,600,000 molecules (35, 190 and 234 g l ) of para-dichorobenzene, bisphenol A and trinitrotoluene, respectively.H ost-guest phenomena that involve the uptake of gases and small molecules are associated with the supramolecular chemistry of soluble capsules, cages and containers [1][2][3][4][5] or, alternatively, with heterogeneous reactions of porous solid-state materials such as zeolites 6 and metal-organic frameworks 7 . Only now, however, are organized assemblies of metal nanoparticles beginning to serve in a similar capacity as hosts for molecular guests. In organic solvents, for example, light-induced dipoledipole interactions between gold nanoparticles with azobenzenefunctionalized thiolate ligands were recently used to entrap and catalyse the reactions of polar and alkylaromatic substrates 8 . By design, substrates were entrapped during nanoparticle aggregation to overcome the poor uptake and diffusion of molecular guests into colloidal nanocrystal assemblies. However, the uptake of molecular guests, a trait of supramolecular and solid-state chemistry, has so far not been achieved for colloidal nanoparticle assemblies.For that to occur, a thermodynamically favourable driving force must be combined with a porous structure whose interior architecture features host cavities, along with pathways for the effective diffusion of molecular guests from the exterior (bulk solution) to host domains deeply buried in the assembly's interior. If this were achieved, colloidal metal-nanoparticle assemblies could emerge as a new class of functional nano-engineered structures that are uniquely positioned between supramolecular containers and porous solid-state materials.We report a new class of functional assemblies, wherein the hydrophobic effect 9,10 drives the spontaneous uptake of alkyl and alkylaromatic guests 11 by porous 200 nm diameter supraspheres whose host capacities are orders of magnitude larger than those of individual cages or containers. On a mass-per-volume basis, the level of uptake rivals those of zeolites and metal-organic frameworks, which, for methane at elevated pressures, r...

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“…The diffusion coefficients of the solutes in the bulk solvent were determined by the Wilke-Chang equation [46] (equation 15), where the solute molar volume ( ) at the boiling point was determined using a group contribution method as presented by Zhao et al [47]. In cases where the pore diameters are significantly small and similar to the solvent diameter (d p ≈ d solv ), pore viscosities need to be corrected since they are significantly higher than the bulk values ( 0 ) [38] (Equation 16).…”

Section: Equation 13mentioning

confidence: 99%

Hybrid polymer/MOF membranes for Organic Solvent Nanofiltration (OSN): Chemical modification and the quest for perfection

Campbell

Burgal

Székely

et al. 2016

Journal of Membrane Science

145

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Fast Calculation of van der Waals Volume as a Sum of Atomic and Bond Contributions and Its Application to Drug Compounds

Cited by 603 publications

References 21 publications

Structure of the Catalytic Domain of the Class I Polyhydroxybutyrate Synthase from Cupriavidus necator

Structure of the Catalytic Domain of the Class I Polyhydroxybutyrate Synthase from Cupriavidus necator

Host–guest chemistry with water-soluble gold nanoparticle supraspheres

Hybrid polymer/MOF membranes for Organic Solvent Nanofiltration (OSN): Chemical modification and the quest for perfection

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