Biomedical subjects

Aswin Sai Narain Seshasayee

Publications and source records attributed to Aswin Sai Narain Seshasayee.

6 recordsLinked to original sources

PubMed2025

Evolution of Transcription Factor-containing Superfamilies in Eukaryotes.

Regulation of gene expression helps determine various phenotypes in most cellular life forms. It is orchestrated at different levels and at the point of transcription initiation by transcription factors (TFs). TFs bind to DNA through domains that are evolutionarily related, by shared membership of the same superfamilies (TF-SFs), to those found in other nucleic acid binding and protein-binding functions (nTFs for non-TFs). Here we ask how TF DNA binding sequence families in eukaryotes have evolved in relation to their nTF relatives. TF numbers scale by power law with the total number of protein-coding genes differently in different clades, with fungi usually showing sub-linear powers whereas chordates show super-linear scaling. The LECA probably encoded a complex regulatory machinery with both TFs and nTFs, but with an excess of nTFs when compared to the relative distribution of TFs and nTFs in extant organisms. Losses drive the evolution of TFs and nTFs, with the possible exception of TFs in animals for some tree topologies. TFs are highly dynamic in evolution, showing higher gain and loss rates than nTFs in some TF-SFs though both are conserved to similar extents. Gains of TFs and nTFs are driven by the appearance of a large number of new sequence clusters in a small number of nodes, which determine the presence of as many as a third of extant TFs and nTFs as well as the relative presence of TFs and nTFs. Whereas nodes showing explosion of TF numbers belong to multicellular clades, those for nTFs lie among the fungi and the protists.

Transcription Factors↗

PubMed2006

Social behavior of the yeast protein-protein interaction network.

Protein-protein interaction networks are useful in contextual annotation of protein function and in general to achieve a system-level understanding of cellular behavior. This work reports on the social behavior of the yeast protein-protein interaction network and concludes that it is non-random. This work, while providing an analysis of organization of genes into functional societies, can potentially be useful in assessing the accuracy of contextual gene annotation based on such interaction networks.

Computational Biology↗

PubMed2005

Role of hydrophobic interactions and salt-bridges in beta-hairpin folding.

Beta-hairpins are the simplest form of beta-sheets which, due to the presence of long-range interactions, can be considered as tertiary structures. Molecular dynamics simulation is a powerful tool that can unravel whole pathways of protein folding/unfolding at atomic resolution. We have performed several molecular dynamics simulations, to a total of over 250 ns, of a beta-hairpin peptide in water using GROMACS. We show that hydrophobic interactions are necessary for initiating the folding of the peptide. Once formed, the peptide is stabilized by hydrogen bonds and disruption of hydrophobic interactions in the folded peptide does not denature the structure. In the absence of hydrophobic interactions, the peptide fails to fold. However, the introduction of a salt-bridge compensates for the loss of hydrophobic interactions to a certain extent.

Computer Simulation↗

PubMed2005

Evidence of a double-lid movement in Pseudomonas aeruginosa lipase: insights from molecular dynamics simulations.

Pseudomonas aeruginosa lipase is a 29-kDa protein that, following the determination of its crystal structure, was postulated to have a lid that stretched between residues 125 and 148. In this paper, using molecular dynamics simulations, we propose that there exists, in addition to the above-mentioned lid, a novel second lid in this lipase. We further show that the second lid, covering residues 210-222, acts as a triggering lid for the movement of the first. We also investigate the role of hydrophobicity in the movement of the lids and show that two residues, Phe214 and Ala217, play important roles in lid movement. To our knowledge, this is the first time that a double-lid movement of the type described in our manuscript has been presented to the scientific community. This work also elucidates the interplay of hydrophobic interactions in the dynamics, and hence the function, of an enzyme.

Computer Simulation↗

PubMed2005

Promoter addresses: revelations from oligonucleotide profiling applied to the Escherichia coli genome.

BACKGROUND: Transcription is the first step in cellular information processing. It is regulated by cis-acting elements such as promoters and operators in the DNA, and trans-acting elements such as transcription factors and sigma factors. Identification of cis-acting regulatory elements on a genomic scale requires computational analysis. RESULTS: We have used oligonucleotide profiling to predict regulatory regions in a bacterial genome. The method has been applied to the Escherichia coli K12 genome and the results analyzed. The information content of the putative regulatory oligonucleotides so predicted is validated through intra-genomic analyses, correlations with experimental data and inter-genome comparisons. Based on the results we have proposed a model for the bacterial promoter. The results show that the method is capable of identifying, in the E.coli genome, cis-acting elements such as TATAAT (sigma70 binding site), CCCTAT (1 base relative of sigma32 binding site), CTATNN (LexA binding site), AGGA-containing hexanucleotides (Shine Dalgarno consensus) and CTAG-containing hexanucleotides (core binding sites for Trp and Met repressors). CONCLUSION: The method adopted is simple yet effective in predicting upstream regulatory elements in bacteria. It does not need any prior experimental data except the sequence itself. This method should be applicable to most known genomes. Profiling, as applied to the E.coli genome, picks up known cis-acting and regulatory elements. Based on the profile results, we propose a model for the bacterial promoter that is extensible even to eukaryotes. The model is that the core promoter lies within a plateau of bent AT-rich DNA. This bent DNA acts as a homing segment for the sigma factor to recognize the promoter. The model thus suggests an important role for local landscapes in prokaryotic and eukaryotic gene regulation.

Escherichia coli↗

PubMed2005

High-temperature unfolding of a trp-cage mini-protein: a molecular dynamics simulation study.

BACKGROUND: Trp cage is a recently-constructed fast-folding miniprotein. It consists of a short helix, a 3,10 helix and a C-terminal poly-proline that packs against a Trp in the alpha helix. It is known to fold within 4 ns. RESULTS: High-temperature unfolding molecular dynamics simulations of the Trp cage miniprotein have been carried out in explicit water using the OPLS-AA force-field incorporated in the program GROMACS. The radius of gyration (Rg) and Root Mean Square Deviation (RMSD) have been used as order parameters to follow the unfolding process. Distributions of Rg were used to identify ensembles. CONCLUSION: Three ensembles could be identified. While the native-state ensemble shows an Rg distribution that is slightly skewed, the second ensemble, which is presumably the Transition State Ensemble (TSE), shows an excellent fit. The denatured ensemble shows large fluctuations, but a Gaussian curve could be fitted. This means that the unfolding process is two-state. Representative structures from each of these ensembles are presented here.

Computer Simulation↗