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Journal ArticleDOI

In-silico analysis of Betaine Aldehyde Dehydrogenase2 of Oryza sativa and significant mutations responsible for fragrance

10 Jan 2013-Journal of Plant Interactions (Taylor & Francis Group)-Vol. 8, Iss: 4, pp 321-333
TL;DR: In this study, an in-silico approach to explore the interaction behavior of model structures of native and mutant BADH2 enzyme and a substrate GAB-ald, which is responsible for fragrance in rice found that the BADH 2 N162A was considered to be the most fragrant form.
Abstract: Fragrance in rice plays an important characteristic feature in determining the quality of rice. 2-Acetyl-1-pyrroline (2AP) compound is responsible for the fragrance in rice. Betaine-aldehyde-dehydr...
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Journal ArticleDOI
TL;DR: In this article, the authors implemented computational analysis to filter the most probable mutation that might be associated with OCA3, and found R326H and R356Q as most deleterious and disease associated by using PolyPhen 2.0, SIFT, PANTHER, I-mutant 3, PhD-SNP, SNP&GO, Pmut, and Mutpred tools.
Abstract: Oculocutaneous albinism type III (OCA3), caused by mutations of TYRP1 gene, is an autosomal recessive disorder characterized by reduced biosynthesis of melanin pigment in the hair, skin, and eyes. The TYRP1 gene encodes a protein called tyrosinase-related protein-1 (Tyrp1). Tyrp1 is involved in maintaining the stability of tyrosinase protein and modulating its catalytic activity in eumelanin synthesis. Tyrp1 is also involved in maintenance of melanosome structure and affects melanocyte proliferation and cell death. In this work we implemented computational analysis to filter the most probable mutation that might be associated with OCA3. We found R326H and R356Q as most deleterious and disease associated by using PolyPhen 2.0, SIFT, PANTHER, I-mutant 3.0, PhD-SNP, SNP&GO, Pmut, and Mutpred tools. To understand the atomic arrangement in 3D space, the native and mutant (R326H and R356Q) structures were modelled. Finally the structural analyses of native and mutant Tyrp1 proteins were investigated using molecular dynamics simulation (MDS) approach. MDS results showed more flexibility in native Tyrp1 structure. Due to mutation in Tyrp1 protein, it became more rigid and might disturb the structural conformation and catalytic function of the structure and might also play a significant role in inducing OCA3. The results obtained from this study would facilitate wet-lab researches to develop a potent drug therapies against OCA3.

72 citations

Journal ArticleDOI
TL;DR: The results obtained in this study will serve as a starting point for future investigation on cancer research in association to CENPX protein.
Abstract: Genome sequencing has overflowed the databases with huge amount of SNP data. Although the amount of detected single nucleotide polymorphisms (SNPs) is rising exponentially every day, we still lag behind in characterization techniques. Implementing computational platforms to determine the pathogenecity associated with the SNPs can provide a probable solution to this problem. To improve the prediction quality for SNP characterization methods, we implemented machine learning support vector classification method. Total 557 non-synonymous amino acid variants were collected from CENP family proteins, excluding CENPE. Multivariate simulation of associated changes in biological phenomena's for each SNPs was computed through available SNP analysis platforms. Support vector model was designed using training dataset and the raw classification data was subjected to the classification hyperplane. We observed multiple evidences of cancer associated genetic mutations in CENPI, CENPJ, CENPK, CENPL and CENPX protein. The former four proteins have showed positive hits in cosmic database for mutations in tumour samples, but CENPX has never been reported before for the cancer associated outcomes. Since CENPX has been recently classified and not much functional and pathological insight has been, the results obtained in this study will serve as a starting point for future investigation on cancer research in association to CENPX protein.

15 citations

Journal ArticleDOI
TL;DR: Structural and dynamic insights of BADH2 obtained here could play a role in the improvement of rice fragrance, which could lead to an enhancement in rice quality and market price.
Abstract: Betaine aldehyde dehydrogenase 2 (BADH2) plays a key role in the accumulation of 2-acetyl-1-pyrroline (2AP), a fragrant compound in rice (Oryza sativa). BADH2 catalyses the oxidation of aminoaldehydes to carboxylic acids. An inactive BADH2 is known to promote fragrance in rice. The 3D structure and atomic level protein-ligand interactions are currently unknown. Here, the 3D dimeric structure of BADH2 was modeled using homology modeling. Furthermore, two 0.5 µs simulations were performed to explore the nature of BADH2 dimer structurally and dynamically. Each monomer comprises of 3 domains (substrate-binding, NAD+-binding, and oligomerization domains). The NAD+-binding domain is the most mobile. A scissor-like motion was observed between the monomers. Inside the binding pocket, N162 and E260 are tethered by strong hydrogen bonds to residues in close proximity. In contrast, the catalytic C294 is very mobile and interacts occasionally with N162. The flexibility of the nucleophilic C294 could facilitate the attack of free carbonyl on an aldehyde substrate. Key inter-subunit salt bridges contributing to dimerization were also identified. E487, D491, E492, K498, and K502 were found to form strong salt bridges with charged residues on the adjacent monomer. Specifically, the nearly permanent R430-E487 hydrogen bond (>90%) highlights its key role in dimer association. Structural and dynamic insights of BADH2 obtained here could play a role in the improvement of rice fragrance, which could lead to an enhancement in rice quality and market price.

14 citations

Journal ArticleDOI
TL;DR: Both monocot and dicot subunits were found to exploit similar interactions with the substrate and inhibitor molecule as in the case of their closest homologue potato tuber AGPase small subunit, indicating a similar mode of allosteric regulation and catalytic mechanism.
Abstract: ADP-glucose pyrophosphorylase (AGPase) is the first rate limiting enzyme of starch biosynthesis pathway and has been exploited as the target for greater starch yield in several plants. The structure-function analysis and substrate binding specificity of AGPase have provided enormous potential for understanding the role of specific amino acid or motifs responsible for allosteric regulation and catalytic mechanisms, which facilitate the engineering of AGPases. We report the three-dimensional structure, substrate, and inhibitor binding specificity of AGPase small subunit from different monocot and dicot crop plants. Both monocot and dicot subunits were found to exploit similar interactions with the substrate and inhibitor molecule as in the case of their closest homologue potato tuber AGPase small subunit. Comparative sequence and structural analysis followed by molecular docking and electrostatic surface potential analysis reveal that rearrangements of secondary structure elements, substrate, and inhibitor binding residues are strongly conserved and follow common folding pattern and orientation within monocot and dicot displaying a similar mode of allosteric regulation and catalytic mechanism. The results from this study along with site-directed mutagenesis complemented by molecular dynamics simulation will shed more light on increasing the starch content of crop plants to ensure the food security worldwide.

10 citations

Journal ArticleDOI
TL;DR: Three-dimensional model of VuCA1, a gene encoding putative β-carbonic anhydrase gene from cowpea, is reported and quality of the predicted model was analysed with PROCHECK.
Abstract: A gene encoding putative β-carbonic anhydrase gene (CA) from cowpea (Vigna unguiculata L. Walp.) was characterized and designated as VuCA1 (GenBank ID: JQ429799). While the genomic sequence of CA was found to be 1470 bp long with 4 introns, the open reading frame was 990 bp in length. The deduced amino acid sequence of CA contained two characteristic conserved domains, i.e. CSDSRV and EYAVLHLKVSNIVVIGHSACG, which showed high degree of homology with other β-CA genes of angiosperms. We have reported three-dimensional model of VuCA1 and quality of the predicted model was analysed with PROCHECK. Molecular docking of modeled VuCA1 revealed similar binding pockets for different substrates and products. The expression of VuCA1 transcripts was detected in different parts of the cowpea plant, with highest level observed in leaves, followed by flower buds, weak expression in stems, and the weakest in roots. The expression of VuCA1 transcripts of leaves was downregulated by zinc deficiency but upregulated by salt an...

3 citations


Cites methods from "In-silico analysis of Betaine Aldeh..."

  • ...Molecular docking is an important tool to understand the protein–ligand interaction (Kamaraj & Purohit 2013)....

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References
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Journal ArticleDOI
TL;DR: A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score.

88,255 citations


"In-silico analysis of Betaine Aldeh..." refers methods in this paper

  • ...The basic local alignment Search tool (BLAST) (Altschul et al. 1990) found several plant homologous proteins with known 3D structure located at Protein Data Bank (PDB), which was used as the template in homology modeling of native and the mutant (C294A, E260A, and N162A) BADH2....

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  • ...The protein BLAST of BADH2 showed highest sequence identity (76...

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Journal ArticleDOI
TL;DR: Two unusual extensions are presented: Multiscale, which adds the ability to visualize large‐scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales.
Abstract: The design, implementation, and capabilities of an extensible visualization system, UCSF Chimera, are discussed. Chimera is segmented into a core that provides basic services and visualization, and extensions that provide most higher level functionality. This architecture ensures that the extension mechanism satisfies the demands of outside developers who wish to incorporate new features. Two unusual extensions are presented: Multiscale, which adds the ability to visualize large-scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales. Other extensions include Multalign Viewer, for showing multiple sequence alignments and associated structures; ViewDock, for screening docked ligand orientations; Movie, for replaying molecular dynamics trajectories; and Volume Viewer, for display and analysis of volumetric data. A discussion of the usage of Chimera in real-world situations is given, along with anticipated future directions. Chimera includes full user documentation, is free to academic and nonprofit users, and is available for Microsoft Windows, Linux, Apple Mac OS X, SGI IRIX, and HP Tru64 Unix from http://www.cgl.ucsf.edu/chimera/.

35,698 citations


"In-silico analysis of Betaine Aldeh..." refers methods in this paper

  • ...RMSD values between BADH2 model and P. sativum templates were calculated by the use of the Chimera program (Pettersen et al. 2004)....

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Journal ArticleDOI
TL;DR: A new implementation of the molecular simulation toolkit GROMACS is presented which now both achieves extremely high performance on single processors from algorithmic optimizations and hand-coded routines and simultaneously scales very well on parallel machines.
Abstract: Molecular simulation is an extremely useful, but computationally very expensive tool for studies of chemical and biomolecular systems Here, we present a new implementation of our molecular simulation toolkit GROMACS which now both achieves extremely high performance on single processors from algorithmic optimizations and hand-coded routines and simultaneously scales very well on parallel machines The code encompasses a minimal-communication domain decomposition algorithm, full dynamic load balancing, a state-of-the-art parallel constraint solver, and efficient virtual site algorithms that allow removal of hydrogen atom degrees of freedom to enable integration time steps up to 5 fs for atomistic simulations also in parallel To improve the scaling properties of the common particle mesh Ewald electrostatics algorithms, we have in addition used a Multiple-Program, Multiple-Data approach, with separate node domains responsible for direct and reciprocal space interactions Not only does this combination of a

14,032 citations


"In-silico analysis of Betaine Aldeh..." refers methods in this paper

  • ...…3D model of native and the mutant (C294A, E260A, and N162A) BADH2 was refined by MD simulations, using the GROMACS 4.0.5 (Spoel et al. 2005; Hess et al. 2008) running on a single 2.8- GHz Pentium IV IBM machine with 512-MB RAM and running Fedora Core 2 Linux package and GROMOS96 (Baran &…...

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Journal ArticleDOI
TL;DR: The software suite GROMACS (Groningen MAchine for Chemical Simulation) that was developed at the University of Groningen, The Netherlands, in the early 1990s is described, which is a very fast program for molecular dynamics simulation.
Abstract: This article describes the software suite GROMACS (Groningen MAchine for Chemical Simulation) that was developed at the University of Groningen, The Netherlands, in the early 1990s. The software, written in ANSI C, originates from a parallel hardware project, and is well suited for parallelization on processor clusters. By careful optimization of neighbor searching and of inner loop performance, GROMACS is a very fast program for molecular dynamics simulation. It does not have a force field of its own, but is compatible with GROMOS, OPLS, AMBER, and ENCAD force fields. In addition, it can handle polarizable shell models and flexible constraints. The program is versatile, as force routines can be added by the user, tabulated functions can be specified, and analyses can be easily customized. Nonequilibrium dynamics and free energy determinations are incorporated. Interfaces with popular quantum-chemical packages (MOPAC, GAMES-UK, GAUSSIAN) are provided to perform mixed MM/QM simulations. The package includes about 100 utility and analysis programs. GROMACS is in the public domain and distributed (with source code and documentation) under the GNU General Public License. It is maintained by a group of developers from the Universities of Groningen, Uppsala, and Stockholm, and the Max Planck Institute for Polymer Research in Mainz. Its Web site is http://www.gromacs.org.

13,116 citations


"In-silico analysis of Betaine Aldeh..." refers methods in this paper

  • ...…simulation The selected 3D model of native and the mutant (C294A, E260A, and N162A) BADH2 was refined by MD simulations, using the GROMACS 4.0.5 (Spoel et al. 2005; Hess et al. 2008) running on a single 2.8- GHz Pentium IV IBM machine with 512-MB RAM and running Fedora Core 2 Linux package and…...

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  • ...The snapshots were collected at every 5 ps and analyzed with GROMACS analysis tools (Spoel et al. 2005)....

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Journal ArticleDOI
TL;DR: Although the derivation of the algorithm is presented in terms of matrices, no matrix matrix multiplications are needed and only the nonzero matrix elements have to be stored, making the method useful for very large molecules.
Abstract: In this article, we present a new LINear Constraint Solver (LINCS) for molecular simulations with bond constraints. The algorithm is inherently stable, as the constraints themselves are reset instead of derivatives of the constraints, thereby eliminating drift. Although the derivation of the algorithm is presented in terms of matrices, no matrix matrix multiplications are needed and only the nonzero matrix elements have to be stored, making the method useful for very large molecules. At the same accuracy, the LINCS algorithm is three to four times faster than the SHAKE algorithm. Parallelization of the algorithm is straightforward. (C) 1997 John Wiley & Sons, Inc.

12,699 citations

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