Biology subjects

Verma, N.

Publications and source records attributed to Verma, N..

43 records · Page 3Linked to original sources

bioRxiv2020

Computational investigation for modelling the protein-protein interaction of TasA(28-261)with TapA(33-253); a decisive process in biofilm formation by Bacillus subtilis

Biofilms have significant role in microbial persistence, antibiotic resistance and chronic infections; consequently, there is a pressing need for development of novel "anti-biofilm strategies". One of the fundamental mechanisms involved in biofilm formation is protein-protein interactions of amyloid like proteins (ALPs) in extracellular matrix. Such interactions could be potential targets for development of novel anti-biofilm strategies; therefore, assessing the structural features of these interactions could be of great scientific value. Characterization of biomolecular interaction with conventional structure biology tools including X-Ray diffraction and Nuclear Magnetic Resonance is technically challenging, expensive and time-consuming. In contrast, modelling such interactions is time-efficient, economical and might provide deeper understanding of structural basis of interactions. Therefore, during the present study, protein-protein interaction of TasA(28-261)-TapA(33-253) (which is a decisive process for biofilm formation by Bacillus subtilis) was modeled using in silico approaches viz., molecular modelling, protein-protein docking and molecular dynamics simulations. Results identified amino-acid residues present within intrinsically disordered regions of both proteins to be critical for interaction. These results were further supported with PCA and FEL analyses. Results presented here represent novel finding and we hypothesize that aa identified during the present study could be targeted for inhibition of biofilm formation by B. subtilis.

bioinformatics↗

bioRxiv2020

Role of Sulphate Transporter (PiSulT) of Endophytic Fungus Serendipita indica in Plant Growth and Development

Sulfur is an important macronutrient required for the growth, development of plants and is a key component of many metabolic pathways. We have functionally characterized a high-affinity sulphate transporter (PiSulT) from an endophytic fungus Serendipita indica. The PiSulT belongs to the major facilitator superfamily (MFS) of membrane transporter. The PiSulT functionally complements the yeast sulphate transporter mutant HK14. PiSulT is a high-affinity sulphate transporter, having Km 15M. We found enhanced expression of PiSulT in external fungal hyphae which helps the fungus in the acquisition of sulphate from the soil. When knockdown (KD)-PiSulT-P.indica colonized with the plant, it results in an 8-fold reduction in the transfer of sulphate to the colonized plants as compared to the plants colonized with the WT S. indica, which suggests that PiSulT is playing a role in sulphate transfer from soil to host plant. Further, plants colonized with the WT S. indica were found to be healthy in comparison to the plants colonized with the KD-PiSulT-P.indica. Additionally, S. indica colonization provides a positive effect on total sulfur content and on plant metabolites like sulfate ions and glutathione, particularly under low sulphate condition. We observed that the expression of sulfur assimilation pathway genes of S. indica and plant is dependent on the availability of sulphate and on the colonization with the plant. Our study highlights the importance of PiSulT in the improvement of sulfur nutrition of host plant particularly under low sulphate condition and in plant growth development. This study will open new vistas to use S. indica as a bio-fertilizer in the sulphate deficient field to improve crop production. One-Sentence SummaryHigh-affinity sulphate transporter of Serendipita indica (PiSulT) transfer sulphate from soil to plant under low sulphate condition and improve plant growth and development.

microbiology↗

bioRxiv2019

SSnet - Secondary Structure based End-to-End Learning model for Protein-Ligand Interaction Prediction

Computational prediction of Protein-Ligand Interaction (PLI) is an important step in the modern drug discovery pipeline as it mitigates the cost, time, and resources required to screen novel therapeutics. Deep Neural Networks (DNN) have recently shown excellent performance in PLI prediction. However, the performance is highly dependent on protein and ligand features utilized for the DNN model. Moreover, in current models, the deciphering of how protein features determine the underlying principles that govern PLI is not trivial. In this work, we developed a DNN framework named SSnet that utilizes secondary structure information of proteins extracted as the curvature and torsion of the protein backbone to predict PLI. We demonstrate the performance of SSnet by comparing against a variety of currently popular machine and non-machine learning models using various metrics. We visualize the intermediate layers of SSnet to show a potential latent space for proteins, in particular to extract structural elements in a protein that the model finds influential for ligand binding, which is one of the key features of SSnet. We observed in our study that SSnet learns information about locations in a protein where a ligand can bind including binding sites, allosteric sites and cryptic sites, regardless of the conformation used. We further observed that SSnet is not biased to any specific molecular interaction and extracts the protein fold information critical for PLI prediction. Our work forms an important gateway to the general exploration of secondary structure based deep learning, which is not just confined to protein-ligand interactions, and as such will have a large impact on protein research while being readily accessible for de novo drug designers as a standalone package.

bioinformatics↗

bioRxiv2019

Mycobacterial OtsA structures reveal an allosteric site regulated by 2-oxoglutarate and 2-phosphoglycerate and the mechanism for substrate preference.

Trehalose is an essential disaccharide for mycobacteria and a key constituent of several cell wall glycolipids with fundamental roles in pathogenesis. Mycobacteria possess two pathways for trehalose biosynthesis. However, only the OtsAB pathway was found to be essential in M. tuberculosis, with marked growth and virulence defects of OtsA mutants and strict essentiality of OtsB2. Herein, we report the first mycobacterial OtsA structures from M. thermoresistibile in both apo and ligand-bound forms. Structural information reveals three key residues in the mechanism of substrate preference that were further confirmed by site-directed mutagenesis. Additionally, we identify 2-oxoglutarate and 2-phosphoglycerate as allosteric regulators of OtsA. The structural analysis in this work strongly contributed to define the mechanisms for feedback inhibition, show different conformational states of the enzyme and map a new allosteric site.

biochemistry↗

bioRxiv2018

Magnetoelectric materials for miniature, wireless neural stimulation at therapeutic frequencies

A fundamental challenge for bioelectronics is to deliver power to miniature devices inside the body. Wires are common failure points and limit device placement. On the other hand, wireless power by electromagnetic or ultrasound waves must overcome absorption by the body and impedance mismatches between air, bone, and tissue. In contrast, magnetic fields suffer little absorption by the body or differences in impedance at interfaces between air, bone, and tissue. These advantages have led to magnetically-powered stimulators based on induction or magnetothermal effects. However, fundamental limitations in these power transfer technologies have prevented miniature magnetically-powered stimulators from applications in many therapies and disease models because they do not operate in clinical "high-frequency" ranges above 50 Hz. Here we show that magnetoelectric materials - applied in bioelectronic devices - enable miniature magnetically-powered neural stimulators that can operate up to clinically-relevant high-frequencies. As an example, we show that ME neural stimulators can effectively treat the symptoms of a hemi-Parkinsons disease model in freely behaving rodents. We further demonstrate that ME-powered devices can be miniaturized to mm-sized devices, fully implanted, and wirelessly powered in freely behaving rodents. These results suggest that ME materials are an excellent candidate for wireless power delivery that will enable miniature bioelectronics for both clinical and research applications.

bioengineering↗

bioRxiv2018

Carbonic anhydrase network of genes trigger cytosolic pH enabling differentiation from quiescence

BackgroundCarbonic anhydrase regulates various cellular processes. Intracellular pH flux impacted by carbonic anhydrase alters the enzymes allosteric active site which effects several downstream cellular processes. Earlier, we reported that, the catalytic activity of carbonic anhydrase is independent, but direction of catalysis is affected by cellular pH level. On the other hand carbonic anhydrase alters the cytosolic pH level to facilitate allosteric phosphorylation of proteins which further leads to cellular differentiation through a process being regulated by ncRNAs.\n\nResultsThis study illustrates various ways of cell differentiation/ organ development regulation via carbonic anhydrase interacting network of proteins involved in various cellular processes. It is involved in protein degradation process of other proteins like RPT, 26S proteasome, AT3G15120 and its variant producing ncRNA, etc. Carbonic anhydrase indirectly involved in signaling process along with MAPK in providing innate resistance against biotic and abiotic stresses. It is also indirectly linked to cell membrane transporters like H+-ATPase and V-ATPase B.\n\nConclusionsThough carbonic anhydrase is not directly linked with EMS1 as revealed by network analyses and protein-protein interaction there could be a suitable condition generated by the carbonic anhydrase for EMS1 to be active. Hence, we report that carbonic anhydrase, along with other pH regulating gene complexes plays a major role for making EMS1 functional.

systems biology↗

bioRxiv2018

The cortical dynamics orchestrating skilled prehension

Skillful control of movement is central to our ability to sense and manipulate the world. A large body of work in nonhuman primates has demonstrated that motor cortex provides flexible, time-varying activity patterns that control the arm during reaching and grasping. Previous studies have suggested that these patterns are generated by strong local recurrent dynamics operating autonomously from inputs during movement execution. An alternative possibility is that motor cortex requires coordination with upstream brain regions throughout the entire movement in order to yield these patterns. Here, we developed an experimental preparation in the mouse to directly test these possibilities using optogenetics and electrophysiology during a skilled reach-to-grab-to-eat task. To validate this preparation, we first established that a specific, time-varying pattern of motor cortical activity was required to produce coordinated movement. Next, in order to disentangle the contribution of local recurrent motor cortical dynamics from external input, we optogenetically held the recurrent contribution constant, then observed how motor cortical activity recovered following the end of this perturbation. Both the neural responses and hand trajectory varied from trial to trial, and this variability reflected variability in external inputs. To directly probe the role of these inputs, we used optogenetics to perturb activity in the thalamus. Thalamic perturbation at the start of the trial prevented movement initiation, and perturbation at any stage of the movement prevented progression of the hand to the target; this demonstrates that input is required throughout the movement. By comparing motor cortical activity with and without thalamic perturbation, we were able to estimate the effects of external inputs on motor cortical population activity. Thus, unlike pattern-generating circuits that are local and autonomous, such as those in the spinal cord that generate left-right alternation during locomotion, the pattern generator for reaching and grasping is distributed across multiple, strongly-interacting brain regions.

neuroscience↗