45 research outputs found
Bio-efficacy of pumpkin phloem lectin on red spider mite, Oligonychus coffeae (Nietner) infesting tea
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Prediction of DNA-binding propensity of proteins by the ball-histogram method using automatic template search
We contribute a novel, ball-histogram approach to DNA-binding propensity prediction of proteins. Unlike state-of-the-art methods based on constructing an ad-hoc set of features describing physicochemical properties of the proteins, the ball-histogram technique enables a systematic, Monte-Carlo exploration of the spatial distribution of amino acids complying with automatically selected properties. This exploration yields a model for the prediction of DNA binding propensity. We validate our method in prediction experiments, improving on state-of-the-art accuracies. Moreover, our method also provides interpretable features involving spatial distributions of selected amino acids
Photo-antagonism of the GABAA receptor
Neurotransmitter receptor trafficking is fundamentally important for synaptic transmission and neural network activity. GABAA receptors and inhibitory synapses are vital components of brain function, yet much of our knowledge regarding receptor mobility and function at inhibitory synapses is derived indirectly from using recombinant receptors, antibody-tagged native receptors and pharmacological treatments. Here we describe the use of a set of research tools that can irreversibly bind to and affect the function of recombinant and neuronal GABAA receptors following ultraviolet photoactivation. These compounds are based on the competitive antagonist gabazine and incorporate a variety of photoactive groups. By using site-directed mutagenesis and ligand-docking studies, they reveal new areas of the GABA binding site at the interface between receptor β and α subunits. These compounds enable the selected inactivation of native GABAA receptor populations providing new insight into the function of inhibitory synapses and extrasynaptic receptors in controlling neuronal excitation
Defining an Essence of Structure Determining Residue Contacts in Proteins
The network of native non-covalent residue contacts determines the three-dimensional structure of a protein. However, not all contacts are of equal structural significance, and little knowledge exists about a minimal, yet sufficient, subset required to define the global features of a protein. Characterisation of this “structural essence” has remained elusive so far: no algorithmic strategy has been devised to-date that could outperform a random selection in terms of 3D reconstruction accuracy (measured as the Ca RMSD). It is not only of theoretical interest (i.e., for design of advanced statistical potentials) to identify the number and nature of essential native contacts—such a subset of spatial constraints is very useful in a number of novel experimental methods (like EPR) which rely heavily on constraint-based protein modelling. To derive accurate three-dimensional models from distance constraints, we implemented a reconstruction pipeline using distance geometry. We selected a test-set of 12 protein structures from the four major SCOP fold classes and performed our reconstruction analysis. As a reference set, series of random subsets (ranging from 10% to 90% of native contacts) are generated for each protein, and the reconstruction accuracy is computed for each subset. We have developed a rational strategy, termed “cone-peeling” that combines sequence features and network descriptors to select minimal subsets that outperform the reference sets. We present, for the first time, a rational strategy to derive a structural essence of residue contacts and provide an estimate of the size of this minimal subset. Our algorithm computes sparse subsets capable of determining the tertiary structure at approximately 4.8 Å Ca RMSD with as little as 8% of the native contacts (Ca-Ca and Cb-Cb). At the same time, a randomly chosen subset of native contacts needs about twice as many contacts to reach the same level of accuracy. This “structural essence” opens new avenues in the fields of structure prediction, empirical potentials and docking
The concept of RNA-assisted protein folding: the role of tRNA
We suggest that tRNA actively participates in the transfer of 3D information from mRNA to peptides - in addition to its well-known, "classical" role of translating the 3-letter RNA codes into the one letter protein code. The tRNA molecule displays a series of thermodynamically favored configurations during translation, a movement which places the codon and coded amino acids in proximity to each other and make physical contact between some amino acids and their codons possible. This specific codon-amino acid interaction of some selected amino acids is necessary for the transfer of spatial information from mRNA to coded proteins, and is known as RNA-assisted protein folding
Inference of Co-Evolving Site Pairs: an Excellent Predictor of Contact Residue Pairs in Protein 3D structures
Residue-residue interactions that fold a protein into a unique
three-dimensional structure and make it play a specific function impose
structural and functional constraints on each residue site. Selective
constraints on residue sites are recorded in amino acid orders in homologous
sequences and also in the evolutionary trace of amino acid substitutions. A
challenge is to extract direct dependences between residue sites by removing
indirect dependences through other residues within a protein or even through
other molecules. Recent attempts of disentangling direct from indirect
dependences of amino acid types between residue positions in multiple sequence
alignments have revealed that the strength of inferred residue pair couplings
is an excellent predictor of residue-residue proximity in folded structures.
Here, we report an alternative attempt of inferring co-evolving site pairs from
concurrent and compensatory substitutions between sites in each branch of a
phylogenetic tree. First, branch lengths of a phylogenetic tree inferred by the
neighbor-joining method are optimized as well as other parameters by maximizing
a likelihood of the tree in a mechanistic codon substitution model. Mean
changes of quantities, which are characteristic of concurrent and compensatory
substitutions, accompanied by substitutions at each site in each branch of the
tree are estimated with the likelihood of each substitution. Partial
correlation coefficients of the characteristic changes along branches between
sites are calculated and used to rank co-evolving site pairs. Accuracy of
contact prediction based on the present co-evolution score is comparable to
that achieved by a maximum entropy model of protein sequences for 15 protein
families taken from the Pfam release 26.0. Besides, this excellent accuracy
indicates that compensatory substitutions are significant in protein evolution.Comment: 17 pages, 4 figures, and 4 tables with supplementary information of 5
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Protein 3D Structure Computed from Evolutionary Sequence Variation
The evolutionary trajectory of a protein through sequence space is constrained by its function. Collections of sequence homologs record the outcomes of millions of evolutionary experiments in which the protein evolves according to these constraints. Deciphering the evolutionary record held in these sequences and exploiting it for predictive and engineering purposes presents a formidable challenge. The potential benefit of solving this challenge is amplified by the advent of inexpensive high-throughput genomic sequencing
Structure networks of E. coli glutaminyl-tRNA synthetase: effects of ligand binding
It is well known that proteins undergo backbone as well as side chain conformational changes upon ligand binding, which is not necessarily confined to the active site. Both the local and the global conformational changes brought out by ligand-binding have been extensively studied earlier. However, the global changes have been reported mainly at the protein backbone level. Here we present a method that explicitly takes into account the side chain interactions, yet providing a global view of the ligand-induced conformational changes. This is achieved through the analysis of Protein Structure Networks (PSN), constructed from the noncovalent side chain interactions in the protein. Here, E. coli Glutaminyl-tRNA synthetase (GlnRS) in the ligand-free and different ligand-bound states is used as a case study to assess the effect of binding of tRNA, ATP, and the amino acid Gln to GlnRS. The PSNs are constructed on the basis of the strength of noncovalent interactions existing between the side chains of amino acids. The parameters like the size of the largest cluster, edge to node ratio, and the total number of hubs are used to quantitatively assess the structure network changes. These network parameters have effectively captured the ligand-induced structural changes at a global structure network level. Hubs, the highly connected amino acids, are also identified from these networks. Specifically, we are able to characterize different types of hubs based on the comparison of structure networks of the GlnRS system. The differences in the structure networks in both the presence and the absence of the ligands are reflected in these hubs. For instance, the characterization of hubs that are present in both the ligand-free and all the ligand-bound GlnRS (the invariant hubs) might implicate their role in structural integrity. On the other hand, identification of hubs unique to a particular ligand-bound structure (the exclusive hubs) not only highlights the structural differences mediated by ligand-binding at the structure network level, but also highlights significance of these amino acids hubs in binding to the ligand and catalyzing the biochemical function. Further, the hubs identified from this study could be ideal targets for mutational studies to ascertain the ligand-induced structure-function relationships in E. coli GlnRS. The formalism used in this study is simple and can be applied to other protein-ligands in general to understand the allosteric changes mediated by the binding of ligands