Saraswathi Vishveshwara

Bio: Saraswathi Vishveshwara is an academic researcher from Indian Institute of Science. The author has contributed to research in topics: Protein structure & Ab initio. The author has an hindex of 22, co-authored 77 publications receiving 2129 citations.

A study of communication pathways in methionyl- tRNA synthetase by molecular dynamics simulations and structure network analysis

Abstract: The enzymes of the family of tRNA synthetases perform their functions with high precision by synchronously recognizing the anticodon region and the aminoacylation region, which are separated by \approx 70 \AA in space. This precision in function is brought about by establishing good communication paths between the two regions. We have modeled the structure of the complex consisting of Escherichia coli methionyl-tRNA synthetase (MetRS), tRNA, and the activated methionine. Molecular dynamics simulations have been performed on the modeled structure to obtain the equilibrated structure of the complex and the cross-correlations between the residues in MetRS have been evaluated. Furthermore, the network analysis on these simulated structures has been carried out to elucidate the paths of communication between the activation site and the anticodon recognition site. This study has provided the detailed paths of communication, which are consistent with experimental results. Similar studies also have been carried out on the complexes (MetRS + activated methonine) and (MetRS + tRNA) along with ligand-free native enzyme. A comparison of the paths derived from the four simulations clearly has shown that the communication path is strongly correlated and unique to the enzyme complex, which is bound to both the tRNA and the activated methionine. The details of the method of our investigation and the biological implications of the results are presented in this article. The method developed here also could be used to investigate any protein system where the function takes place through long-distance communication.

Intra and inter-molecular communications through protein structure network.

Abstract: Communication within and across proteins is crucial for the biological functioning of proteins. Experiments such as mutational studies on proteins provide important information on the amino acids, which are crucial for their function. However, the protein structures are complex and it is unlikely that the entire responsibility of the function rests on only a few amino acids. A large fraction of the protein is expected to participate in its function at some level or other. Thus, it is relevant to consider the protein structures as a completely connected network and then deduce the properties, which are related to the global network features. In this direction, our laboratory has been engaged in representing the protein structure as a network of non-covalent connections and we have investigated a variety of problems in structural biology, such as the identification of functional and folding clusters, determinants of quaternary association and characterization of the network properties of protein structures. We have also addressed a few important issues related to protein dynamics, such as the process of oligomerization in multimers, mechanism on protein folding, and ligand induced communications (allosteric effect). In this review we highlight some of the investigations which we have carried out in the recent past. A review on protein structure graphs was presented earlier, in which the focus was on the graphs and graph spectral properties and their implementation in the study of protein structure graphs/networks (PSN). In this article, we briefly summarize the relevant parts of the methodology and the focus is on the advancement brought out in the understanding of protein structure-function relationships through structure networks. The investigations of structural/biological problems are divided into two parts, in which the first part deals with the analysis of PSNs based on static structures obtained from x-ray crystallography. The second part highlights the changes in the network, associated with biological functions, which are deduced from the network analysis on the structures obtained from molecular dynamics simulations.

“Bioinformatics” 특집을 내면서

Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

Methods in Enzymology.

Abstract: I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

[19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors

Abstract: Publisher Summary This chapter discusses the integrated methods for the construction of three-dimensional models and computational probing of structure–function relations in G protein-coupled receptors (GPCR). The rapid pace of cloning and expression of G protein-coupled receptors offers attractive opportunities to probe the structural basis of signal transduction mechanisms at the level of these cell-surface receptors. Major insights have emerged from comparisons and classifications of the amino acid sequences of GPCRs into families defined by evolutionary developments and adapted to perform selective functions. Structural data on GPCRs, based on biochemical, immunological, and biophysical approaches have validated consensus architecture of GPCRs with an extracellular N-terminus, a cytoplasmic C-terminus, and a transmembrane portion comprised of seven-transmembrane helical domains connected by loops. Developments in the molecular modeling and computational exploration of GPCR proteins indicate a tantalizing potential to alleviate some of these difficulties. These expectations are based on the increased rate of success achieved by molecular modeling and computational simulation methods in providing structural insights relevant to the functions of biological molecules.

From Levinthal to pathways to funnels

Abstract: A new view of protein folding kinetics replaces the idea of ‘folding pathways’ with the broader notions of energy landscapes and folding funnels. New experiments are needed to explore them.