3,122 research outputs found
From isomorphism to polymorphism: connecting interzeolite transformations to structural and graph similarity
Zeolites are nanoporous crystalline materials with abundant industrial
applications. Despite sustained research, only 235 different zeolite frameworks
have been realized out of millions of hypothetical ones predicted by
computational enumeration. Structure-property relationships in zeolite
synthesis are very complex and only marginally understood. Here, we apply
structure and graph-based unsupervised machine learning to gain insight on
zeolite frameworks and how they relate to experimentally observed polymorphism
and phase transformations. We begin by describing zeolite structures using the
Smooth Overlap of Atomic Positions method, which clusters crystals with similar
cages and density in a way consistent with traditional hand-selected composite
building units. To also account for topological differences, zeolite crystals
are represented as multigraphs and compared by isomorphism tests. We find that
fourteen different pairs and one trio of known frameworks are graph isomorphic.
Based on experimental interzeolite conversions and occurrence of competing
phases, we propose that the availability of kinetic-controlled transformations
between metastable zeolite frameworks is related to their similarity in the
graph space. When this description is applied to enumerated structures, over
3,400 hypothetical structures are found to be isomorphic to known frameworks,
and thus might be realized from their experimental counterparts. Using a
continuous similarity metric, the space of known zeolites shows additional
overlaps with experimentally observed phase transformations. Hence, graph-based
similarity approaches suggest a venue for realizing novel zeolites from
existing ones by providing a relationship between pairwise structure similarity
and experimental transformations.Comment: 11 pages, 6 figure
Exploring the high-pressure materials genome
A thorough in situ characterization of materials at extreme conditions is
challenging, and computational tools such as crystal structural search methods
in combination with ab initio calculations are widely used to guide experiments
by predicting the composition, structure, and properties of high-pressure
compounds. However, such techniques are usually computationally expensive and
not suitable for large-scale combinatorial exploration. On the other hand,
data-driven computational approaches using large materials databases are useful
for the analysis of energetics and stability of hundreds of thousands of
compounds, but their utility for materials discovery is largely limited to
idealized conditions of zero temperature and pressure. Here, we present a novel
framework combining the two computational approaches, using a simple linear
approximation to the enthalpy of a compound in conjunction with
ambient-conditions data currently available in high-throughput databases of
calculated materials properties. We demonstrate its utility by explaining the
occurrence of phases in nature that are not ground states at ambient conditions
and estimating the pressures at which such ambient-metastable phases become
thermodynamically accessible, as well as guiding the exploration of
ambient-immiscible binary systems via sophisticated structural search methods
to discover new stable high-pressure phases.Comment: 14 pages, 6 figure
Magnetism, FeS colloids, and Origins of Life
A number of features of living systems: reversible interactions and weak
bonds underlying motor-dynamics; gel-sol transitions; cellular connected
fractal organization; asymmetry in interactions and organization; quantum
coherent phenomena; to name some, can have a natural accounting via
interactions, which we therefore seek to incorporate by expanding the horizons
of `chemistry-only' approaches to the origins of life. It is suggested that the
magnetic 'face' of the minerals from the inorganic world, recognized to have
played a pivotal role in initiating Life, may throw light on some of these
issues. A magnetic environment in the form of rocks in the Hadean Ocean could
have enabled the accretion and therefore an ordered confinement of
super-paramagnetic colloids within a structured phase. A moderate H-field can
help magnetic nano-particles to not only overcome thermal fluctuations but also
harness them. Such controlled dynamics brings in the possibility of accessing
quantum effects, which together with frustrations in magnetic ordering and
hysteresis (a natural mechanism for a primitive memory) could throw light on
the birth of biological information which, as Abel argues, requires a
combination of order and complexity. This scenario gains strength from
observations of scale-free framboidal forms of the greigite mineral, with a
magnetic basis of assembly. And greigite's metabolic potential plays a key role
in the mound scenario of Russell and coworkers-an expansion of which is
suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed
Krishnaswami Alladi, Springer 201
A Score of the Ability of a Three-Dimensional Protein Model to Retrieve Its Own Sequence as a Quantitative Measure of Its Quality and Appropriateness
BACKGROUND: Despite the remarkable progress of bioinformatics, how the primary structure of a protein leads to a three-dimensional fold, and in turn determines its function remains an elusive question. Alignments of sequences with known function can be used to identify proteins with the same or similar function with high success. However, identification of function-related and structure-related amino acid positions is only possible after a detailed study of every protein. Folding pattern diversity seems to be much narrower than sequence diversity, and the amino acid sequences of natural proteins have evolved under a selective pressure comprising structural and functional requirements acting in parallel. PRINCIPAL FINDINGS: The approach described in this work begins by generating a large number of amino acid sequences using ROSETTA [Dantas G et al. (2003) J Mol Biol 332:449-460], a program with notable robustness in the assignment of amino acids to a known three-dimensional structure. The resulting sequence-sets showed no conservation of amino acids at active sites, or protein-protein interfaces. Hidden Markov models built from the resulting sequence sets were used to search sequence databases. Surprisingly, the models retrieved from the database sequences belonged to proteins with the same or a very similar function. Given an appropriate cutoff, the rate of false positives was zero. According to our results, this protocol, here referred to as Rd.HMM, detects fine structural details on the folding patterns, that seem to be tightly linked to the fitness of a structural framework for a specific biological function. CONCLUSION: Because the sequence of the native protein used to create the Rd.HMM model was always amongst the top hits, the procedure is a reliable tool to score, very accurately, the quality and appropriateness of computer-modeled 3D-structures, without the need for spectroscopy data. However, Rd.HMM is very sensitive to the conformational features of the models' backbone
Structure based inhibitor design targeting glycogen phosphorylase b. Virtual screening, synthesis, biochemical and biological assessment of novel N-acyl-ÎČ-d-glucopyranosylamines
Glycogen phosphorylase (GP) is a validated target for the development of new type 2 diabetes treatments. Exploiting the Zinc docking database, we report the in silico screening of 1888 ÎČ- D-glucopyranose-NH-CO-R putative GP inhibitors differing only in their R groups. CombiGlide and GOLD docking programs with different scoring functions were employed with the best performing methods combined in a âconsensus scoringâ approach to ranking of ligand binding affinities for the active site. Six selected candidates from the screening were then synthesized and their inhibitory potency was assessed both in vitro and ex vivo. Their inhibition constantsâ values, in vitro, ranged from 5 to 377 ”M while two of them were effective at causing inactivation of GP in rat hepatocytes at low ”M concentrations. The crystal structures of GP in complex with the inhibitors were defined and provided the structural basis for their inhibitory potency and data for further structure based design of more potent inhibitors
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Adaptations of Escherichia coli strains to oxidative stress are reflected in properties of their structural proteomes.
BACKGROUND:The reconstruction of metabolic networks and the three-dimensional coverage of protein structures have reached the genome-scale in the widely studied Escherichia coli K-12 MG1655 strain. The combination of the two leads to the formation of a structural systems biology framework, which we have used to analyze differences between the reactive oxygen species (ROS) sensitivity of the proteomes of sequenced strains of E. coli. As proteins are one of the main targets of oxidative damage, understanding how the genetic changes of different strains of a species relates to its oxidative environment can reveal hypotheses as to why these variations arise and suggest directions of future experimental work. RESULTS:Creating a reference structural proteome for E. coli allows us to comprehensively map genetic changes in 1764 different strains to their locations on 4118 3D protein structures. We use metabolic modeling to predict basal ROS production levels (ROStype) for 695 of these strains, finding that strains with both higher and lower basal levels tend to enrich their proteomes with antioxidative properties, and speculate as to why that is. We computationally assess a strain's sensitivity to an oxidative environment, based on known chemical mechanisms of oxidative damage to protein groups, defined by their localization and functionality. Two general groups - metalloproteins and periplasmic proteins - show enrichment of their antioxidative properties between the 695 strains with a predicted ROStype as well as 116 strains with an assigned pathotype. Specifically, proteins that a) utilize a molybdenum ion as a cofactor and b) are involved in the biogenesis of fimbriae show intriguing protective properties to resist oxidative damage. Overall, these findings indicate that a strain's sensitivity to oxidative damage can be elucidated from the structural proteome, though future experimental work is needed to validate our model assumptions and findings. CONCLUSION:We thus demonstrate that structural systems biology enables a proteome-wide, computational assessment of changes to atomic-level physicochemical properties and of oxidative damage mechanisms for multiple strains in a species. This integrative approach opens new avenues to study adaptation to a particular environment based on physiological properties predicted from sequence alone
Novel Cd (II) Coordination Polymers Afforded with EDTA or Trans-1,2-Cdta Chelators and Imidazole, Adenine, or 9-(2-Hydroxyethyl) Adenine Coligands
We thank the âCentre de Tecnologies de la InformaciĂłâ (CTI), Universitat de les Illes Balears
for computational facilities. We also thank all Projects for financial support.Three mixed-ligands of Cd(II) coordination polymers were unintentionally obtained:
{[Cd(”3-EDTA)(Him)·Cd(Him)(H2O)2]·H2O}n (1), {[Cd(”4-CDTA)(Hade)·Cd(Hade)2]}n (2), and
{[Cd(”3-EDTA)(H2O)·Cd(H9heade)(H2O)]·2H2O}n (3), having imidazole (Him), adenine (Hade)
or 9-(2-hydroxyethyl)adenine (9heade) as the N-heterocyclic coligands. Compounds 2 and 3 were
obtained by working with an excess of corresponding N-heterocyclic coligands. The single-crystal
X-ray diffraction structures and thermogravimetric analyses are reported. The chelate moieties in
all three compounds exhibit hepta-coordinated Cd centers, whereas the non-chelated Cd center is
five-coordinated in 1 and six-coordinated in 2 and 3. Him and Hade take part in the seven-coordinated
chelate moieties in 1 and 2, respectively. In contrast, 9heade is unable to replace the aqua ligand
of the chelate [Cd (EDTA) (H2O)] moiety in 3. The thermogravimetric analysis (TGA) behavior of
[Cd (H2EDTA) (H2O)]·2H2O in 1 and 3 leads to a residue of CdO, whereas the N-rich compound
2 yields CdO·Cd(NO3)2 as a residue. Density functional theory (DFT) calculations along with
molecular electrostatic potential (MEP) and quantum theory of atoms-in-molecules computations
were performed in adenine (compound 2) and (2-hydroxyethyl)adenine (compound 3) to analyze
how the strength of the H-bonding and Ï-stacking interactions, respectively, are affected by their
coordination to the Cd-metal center.Excellence Network "Metal Ions in Biological Systems" MetalBio
CTQ2017-90802-REDTJunta de Andalucia
FQM-283MICIU /AEI of Spain
CTQ2017-85821-
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