Protein structure prediction continues to pose multiple challenges despite outstanding progress that is largely attributable to the use of novel machine learning techniques. One of the widely used ...representations of local 3D structure—protein blocks (PBs)—can be treated in a similar way to secondary structure classes. Here, we present a new approach for predicting local conformation in terms of PB classes solely from amino acid sequences. We apply the RMSD metric to ensure unambiguous future 3D protein structure recovery. The selection of statistically assessed features is a key component of the proposed method. We suggest that ML input features should be created from the statistically significant predictors that are derived from the amino acids’ physicochemical properties and the resolved structures’ statistics. The statistical significance of the suggested features was assessed using a stepwise regression analysis that permitted the evaluation of the contribution and statistical significance of each predictor. We used the set of 380 statistically significant predictors as a learning model for the regression neural network that was trained using the PISCES30 dataset. When using the same dataset and metrics for benchmarking, our method outperformed all other methods reported in the literature for the CB513 nonredundant dataset (for the PBs, Q16 = 81.01%, and for the DSSP, Q3 = 85.99% and Q8 = 79.35%).
Local protein structure is usually described via classifying each peptide to a unique class from a set of pre-defined structures. These classifications may differ in the number of structural classes, ...the length of peptides, or class attribution criteria. Most methods that predict the local structure of a protein from its sequence first rely on some classification and only then proceed to the 3D conformation assessment. However, most classification methods rely on homologous proteins' existence, unavoidably lose information by attributing a peptide to a single class or suffer from a suboptimal choice of the representative classes.
To alleviate the above challenges, we propose a method that constructs a peptide's structural representation from the sequence, reflecting its similarity to several basic representative structures. For 5-mer peptides and 16 representative structures, we achieved the Q16 classification accuracy of 67.9%, which is higher than what is currently reported in the literature. Our prediction method does not utilize information about protein homologues but relies only on the amino acids' physicochemical properties and the resolved structures' statistics. We also show that the 3D coordinates of a peptide can be uniquely recovered from its structural coordinates, and show the required conditions under various geometric constraints.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The CHARMM force field for DMPC lipids was modified in order to improve agreement with experiment for a number of important properties of hydrated lipid bilayer. The modification consists in ...introduction of a scaling factor 0.83 for 1-4 electrostatic interactions (between atoms separated by three covalent bonds), which provides correct transgauche ratio in the alkane tails, and recalculation of the headgroup charges on the basis of HF/6-311(d,p) ab-initio computations. Both rigid TIP3P and flexible SPC water models were used with the new lipid model, showing similar results. The new model in a 75 ns simulation has shown a correct value of the area per lipid at zero surface tension, as well as good agreement with the experiment for the electron density, structure factor, and order parameters, including those in the headgroup part of lipids.
We present a new force field parameter set for simulating alkanes. Its functional form and parameters are chosen to make it directly compatible with the AMBER94/99/12 family of force fields ...implemented in the available software. The proposed parameterization enables universal description of both the conformational and thermodynamic properties of linear, branched, and cyclic alkanes. Such unification is achieved by using two essential principles: (1) reduction of the Lennard-Jones radius for all sp3 carbons to 1.75Å; (2) separate optimization of Lennard-Jones well depths for carbons with different degree of substitution. The new parameter set may prove to be optimal for description of alkyl residues in a broad range of biomolecules, from amino acids to lipids with their extended linear tails.
Figure
We have a new force field parameter set applicable to various alkanes, including short and long chains, branches, as well as flexible or rigidly strained rings. The new set proves consistent, in agreement with ab-initio computations and experiment, description of conformational behavior, and thermodynamic physical properties.
Computer‐efficient three‐site water models work with accuracy sufficient to describe the main properties of substance. However, to describe peculiar properties of water, such as the liquid density ...anomaly at 4 °C, multi‐site models are used. Nonetheless, it can be shown that a three‐site model is capable to reproduce the density anomaly as well as correct values for a number of other properties such as dielectric permittivity, heat of vaporization, self‐diffusion coefficient, and valence properties.
Flexible anharmonic three‐site water model for molecular dynamics simulation of liquid has been developed. Distinctive feature of the model is the reproduction of the temperature dependence of liquid density, in particular, the density anomaly at 4 °C. As well as it adequately reproduces values of a number of other properties such as dielectric permittivity, heat of vaporization, self‐diffusion coefficient, and valence properties. Being a three‐site model, it is subject for easy and efficient program implementation.
The ability of platelets to carry out their hemostatic function can be impaired in a wide range of inherited and acquired conditions: trauma, surgery, inflammation, pre-term birth, sepsis, ...hematological malignancies, solid tumors, chemotherapy, autoimmune disorders, and many others. Evaluation of this impairment is vitally important for research and clinical purposes. This problem is particularly pronounced in pediatric patients, where these conditions occur frequently, while blood volume and the choice of blood collection methods could be limited. Here we describe a simple flow cytometry-based screening method of comprehensive whole blood platelet function testing that was validated for a range of pediatric and adult samples (n = 31) in the hematology hospital setting including but not limited to: classic inherited platelet function disorders (Glanzmann's thrombasthenia; Bernard-Soulier, Wiscott-Aldrich, and Hermasky-Pudlak syndromes, MYH9-dependent thrombocytopenia), healthy and pre-term newborns, acute and chronic immune thrombocytopenia, chronic lympholeukemia, effects of therapy on platelet function, etc. The method output includes levels of forward and side scatter, levels of major adhesion and aggregation glycoproteins Ib and IIb-IIIa, active integrins' level based on PAC-1 binding, major alpha-granule component P-selectin, dense granule function based on mepacrine uptake and release, and procoagulant activity quantified as a percentage of annexin V-positive platelets. This analysis is performed for both resting and dual-agonist-stimulated platelets. Preanalytical and analytical variables are provided and discussed. Parameter distribution within the healthy donor population for adults (n = 72) and children (n = 17) is analyzed.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
Parasitic life-strategies in the phylum Nematoda (roundworms) are remarkably diverse and intricate in terms of evolution and taxonomy. By analysing novel rDNA data obtained on rare ...host-associated groups with unusual biology, we reveal paraphyly of the last major taxon with uncertain higher-rank classification that united solely parasitic nematodes (Marimermithida) to show that primarily marine parasitism only emerged independently and repeatedly in a few free-living lineages. We report secondary seaward ingression of land-based parasites (Mermithida) via invading hosts in the subtidal zone to illustrate the host-borne scenario of oceanic fish and mammal colonization by primarily terrestrial parasites (Spiruria). We also present the first molecular data on marine nematodes from unicellular hosts (foraminiferan protozoans) to demonstrate the independent origins of exploitative nematode associations at a microscopic scale. We argue that, in contrast with primarily intestinal associations arising from saprotrophy and commensalism, non-intestinal host capture (colonization of host body cavity or internal organs) is likely to be a primary route of transition to truly exploitative parasitism in roundworms. Predispositions to host capture in nematode morphology, ecology and life cycles imply its evolution as part of innate pre-adaptations to crossing environmental boundaries to enable multiple successful transitions to parasitism in the phylum history.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Development of rapid and sensitive immunoassays is a task of great importance in a variety of fields ranging from clinical practice and urgent diagnostics to food quality control and environmental ...monitoring. High attention of researches is paid to methods of screening, selection, and kinetic characterization of antibodies that enable fast, specific, and effective formation of immunocomplexes. Herein, we present a method for direct investigation of kinetics of immunoreagents during developments of express high sensitive lateral flow assays. As model biomolecules to be detected, the following substances were tested: ochratoxin A (OTA), which is one of the most dangerous mycotoxins naturally present in many vegetable raw materials; and heart fatty acids binding protein (hFABP), which is a cardiac marker used in differential diagnosis of acute myocardial infarction. The kinetic constants of association (kon) and dissociation (koff) with monoclonal antibodies are determined along with the corresponding equilibrium constants (KA and KD). The obtained values are as follows: for the anti-OTA antibodies – kon = 4.54*103 M−1s−1; koff = 3.32*10−4 s−1; KA = 1.37*107 M−1; KD = 7.31*10−8 M; and for the anti-hFABP antibodies – kon = 7.28*103 M−1s−1; koff = 1.97*10−4 s−1; KA = 3.70*107 M−1; KD = 2.70*10−8 M. The proposed method can be employed in combination with the immunochromatographic assays based on magnetic biolabels.•Investigation of immunoreagent kinetics for development of express high sensitive lateral flow assays•Kinetic characterization of monoclonal antibodies against OTA and hFABP for their rapid and sensitive detection•Both kinetic and equilibrium constants of association and dissociation are determined
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