Sandhya Premnath TiwariOsaka University | Handai
Sandhya Premnath Tiwari
Doctor of Philosophy
About
29
Publications
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293
Citations
Citations since 2017
Introduction
Additional affiliations
November 2014 - November 2015
May 2009 - September 2009
June 2007 - July 2008
Publications
Publications (29)
The binding of many proteins to their protein partners is tightly regulated via control of their relative intrinsic dynamics during the binding process, a phenomenon which can in turn be modulated. Therefore, investigating the intrinsic dynamics of proteins is necessary to understand function in a comprehensive way. By intrinsic dynamics herein, we...
Many proteins are involved in tightly controlled binding to other proteins by incorporating intrinsic dynamics in the binding process, which can in turn be modulated. Therefore, investigating the intrinsic dynamics of proteins is necessary to understand function in a comprehensive way. By intrinsic dynamics herein we mostly review the vibrational s...
X-ray free-electron laser (XFEL) scattering promises to probe single biomolecular complexes without crystallization, enabling the study of biomolecular structures under near-physiological conditions at room temperature. However, such structural determination of biomolecules is extremely challenging thus far. In addition to the large numbers of diff...
The structural and dynamical characterization of biomolecules holds central importance in the endeavor to understand the molecular mechanisms regulating living systems. However, owing to the inherent heterogeneity of biomolecular interactions within cells, it is often difficult to understand the overall structure and dynamics of biomolecules using...
Cryo-electron microscopy (cryo-EM) single particle analysis has come a long way in achieving atomic-level resolution when imaging biomolecules. In order to obtain the best possible three-dimensional structure in cryo-EM, many parameters have to be carefully considered. Here we address the often-overlooked parameter of the pixel size, which describe...
Background:
Advancements in biophysical experimental techniques have pushed the limits in terms of the types of phenomena that can be characterized, the amount of data that can be produced and the resolution at which we can visualize them. Single particle techniques such as Electron Microscopy (EM) and X-ray free electron laser (XFEL) scattering r...
The intrinsic dynamics of proteins has been suggested to be the most conserved compared to its sequence or structure. As such, the contributing factors to the conservation of dynamics have yet to be determined definitively. Some have suggested that function drives the conservation of protein flexibility, while others have indicated that the overall...
The conservation of the intrinsic dynamics of proteins emerges as we attempt to understand the relationship between sequence, structure and functional conservation. We characterise the conservation of such dynamics in a case where the structure is conserved but function differs greatly. The triosephosphate isomerase barrel fold (TBF), renowned for...
Scheme of the two-dimensional SSE arrangement as viewed from the top of the C-terminal end of each enzyme, identified by PDB ID.
The diversification of the fold occurs with the addition of secondary structure elements, typically at the C-terminal end (smaller circles and triangles). The triangles represent the β-strands, the circles represent the α...
Normalised fluctuations of the five TIM superfamilies and their orthologues.
Green bars show α-helical regions, while red show the β-stranded regions. The sixth panel (bottom right) is a zoomed in profile of 1N55.
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Correlation heatmaps of the main five TBF structures.
Dotted black lines refer to the boundaries of the β-strands, whereas the green dotted lines indicate the helices in between them. The red and blue pixels indicate positive and negative correlations respectively.
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Significant short-range correlations involving β-strands in the five TBF structures.
The Cα atoms of catalytic residues are represented as yellow spheres, the substrate binding by purple spheres, the phosphate binding by cyan spheres, and the metal ion binding by orange spheres. On the left side, there are the top views from the C-terminal end of t...
Sequence identity based on the MUSCLE alignment between the five main TBF proteins from different superfamilies (left) and with the addition of homologous TBF proteins from each of these superfamilies (right).
All of these proteins are identified by their PDB IDs. The colour scale goes from blue to yellow to red, for low (20%) to high (100%) sequen...
Distribution of distant significant correlations in the five TBF structures.
On the left side of the image, we have the top views from the perspective of the C-terminal end, where the respective structures are displayed with the cartoon representation in green, and sticks between each pair of residue positions with significant correlations at least...
Distribution of distant significant distant correlations in the monomeric form (A) and chain A of the dimeric form (B) of 1N55. We have the top views from the perspective of the C-terminal end, where the respective structures are displayed with the cartoon representation in rainbow (N-terminal in blue, C-terminal in red), and sticks between each pa...
Summary of the five main TBF structures studied.
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TBF structures and their additional homologues.
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Oligomeric forms of the TBF enzyme dataset, as defined by the PDB and PISA.
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Sequence representation of the MUSTANG structure alignment of the main five TBF structures.
The α-helices and β-strands are indicated in purple and dark teal, respectively. Red boxes denote parts of the alignment that are conserved between all five sequences.
(PDF)
Normalised deformation energies (calculated over all non-trivial normal modes).
Red shows high deformation energies, while blue shows low energies, with white as the intermediate values. Scale ranges from low (blue) to intermediate (white) to high (red) normalised values of the deformation energies.
(PDF)
Normal mode analysis (NMA) using elastic network models is a reliable and cost-effective computational method to characterise protein flexibility and by extension, their dynamics. Further insight into the dynamics–function relationship can be gained by comparing protein motions between protein homologs and functional classifications. This can be ac...
Evolution and design of protein complexes are almost always viewed through the lens of amino acid mutations at protein interfaces. We showed previously that residues not involved in the physical interaction between proteins make important contributions to oligomerization by acting indirectly or allosterically. In this work, we sought to investigate...
Background:
Elastic network models (ENMs) are based on the simple idea that a protein can be described as a set of particles connected by springs, which can then be used to describe its intrinsic flexibility using, for example, normal mode analysis. Since the introduction of the first ENM by Monique Tirion in 1996, several variants using coarser p...
Oligomerisation is essential for the function of some proteins. The PyrR family of proteins are involved in pyrimidine operon attenuation. They are regulated by the presence of certain nucleotides such as guanosine monophosphate (GMP), which stabilises the tetrameric state. Notably, some members of this family can adopt a tetrameric oligomerisation...
Normal modes analysis (NMA) has been shown to be an effective computational method to study the movements of proteins, especially at the domain level. WEBnm@ (http://apps.cbu.uib.no/webnma/home) is a web-tool which provides access to calculations of these modes on C-alpha atoms of protein structures and various analyses with output as images, plots...
The eight-fold beta/alpha barrel-like fold, first seen in triose-phosphate isomerase (TIM), is a common and versatile fold for proteins. Proteins in this classification have diverse enzymatic functions spanning five of six Enzyme Commission classes. Studies have characterized the sequence, structure, localized dynamics and electrostatics of TIM pro...
Projects
Projects (2)
X-ray free electron laser (XFEL) scattering experiments has been described as the future of structural biology. The technique has several advantages, including its ability to probe a single particle sample without the need for crystallisation, and to produce diffraction data before the sample is destroyed by radiation. However, resolving structures from XFEL diffraction patterns can be challenging due to the phase problem. Considering the novelty of the technique, there is also limited data available to provide initial models that are analogous to an unknown diffraction pattern. Therefore, we consider a strategy to provide efficient interpretation of XFEL data by searching them against a library of simulated 2D projection images from a database of hypothetical biological shapes, built from existing structure data, to obtain an initial structural model.
