Arundhati Banerjee

Molecular level biodegradation of phenol and its derivatives through dmp operon of Pseudomonas putida：A bio-molecular modeling and docking analysis

Participation of Pseudomonas putida-derived methyl phenol (dmp) operon and DmpR protein in the biodegradation of phenol or other harmful, organic, toxic pollutants was investigated at a molecular level. Documentation documents that P. putida has DmpR protein which positively regulates dmp operon in the presence of inducers; like phenols. From the operon, phenol hydroxylase encoded by dmpN gene, participates in degrading phenols after dmp operon is expressed. For the purpose, the 3-D models of the four domains from DmpR protein and of the DNA sequences from the two Upstream Activation Sequences (UAS) present at the promoter region of the operon were demonstrated using discrete molecular modeling techniques. The best modeled structures satisfying their stereo-chemical properties were selected in each of the cases. To stabilize the individual structures, energy optimization was performed. In the presence of inducers, probable interactions among domains and then the two independent DNA structures with the fourth domain were perused by manifold molecular docking simulations. The complex structures were made to be stable by minimizing their overall energy. Responsible amino acid residues, nucleotide bases and binding patterns for the biodegradation, were examined. In the presence of the inducers, the biodegradation process is initiated by the interaction of phe50 from the first protein domain with the inducers. Only after the interaction of the last domain with the DNA sequences individually, the operon is expressed. This novel residue level study is paramount for initiating transcription in the operon; thereby leading to expression of phenol hydroxylase followed by phenol biodegradation.

Molecular modeling, mutational analysis and conformational switching in IL27: An in silico structural insight towards AIDS research

The advancement in proteomics and bioinformatics provokes to discern the molecular-level probe for HIV inhibitor; human interleukin-27 (IL27). Documentation documents that tyrosine residues in IL27 play a pivotal role for interacting with HIV, causing apoptosis of the HIV+ cells. Primarily, 3D structure of human wild-type (WT) IL27 was built through manifold molecular modeling techniques after the satisfaction of stereo-chemical properties. Its essential tyrosine residues were identified. Two mutant models for IL27 were prepared following the similar protocol by first substituting the tyrosine residues with glycine (MT_G) and then with alanine (MT_A) in the WT protein. Molecular dynamics (MD) simulation was performed to obtain a stable conformation. Conformational alterations in WT, MT_G and MT_A (before and after MD simulation) disclosed that MT_A was the steadiest one with the best secondary structure conformation supported by statistical significances. Though huge RMSD variations were observed on superimposing the MT structures on WT individually, the MTs were examined to share similar SCOP/CATH fold with TM-score=0.8, indicating that they retained their functionality even after mutation. Electrostatic surface potential again unveiled MT_A to be the most stable one. MT_A was thereby revealed to be the potent peptide inhibitor for HIV. This probe presents a pathway to investigate and compare the bio-molecular interaction of WT IL27 and MT_A IL27 (strongest model) with HIV in the future. This is the first report regarding the structural biology of IL27 accompanied by alteration at its genetic level and delving into the unknown residue-level and functional biochemistry for bringing about an annihilation towards AIDS.

Molecular Computing and Residual Binding Mode in ERα and bZIP Proteins from Homo Sapiens : An Insight into the Signal Transduction in Breast Cancer Metastasis

The most provoking reason for death in breast cancer patients is the metastasis of breast cancer. Accumulating documentation states that signal transduction in human breast cancers initiate in estrogen-dependent manner with the signaling of estrogen receptor α-subunit (ERα) and XBP-1 (bZIP-domain) proteins. So, molecular level insight into the signaling mechanism is indispensable for future pathological and therapeutic developments. Thus, this current study discloses the stable residual participation of the two crucial human proteins for enhancing the signaling mechanism in breast tumor malignancies. For this purpose, 3D homology models of the respective proteins were prepared after the satisfaction of their stereo-chemical features. The protein–protein interaction was studied and protein complex was energy optimized. Revelation from the stability calculating parameters, solvent accessibility areas and interaction probes led to the inference of the most stable optimized complex and its residual participation (exceptional contribution of polar charged residues) for metastasis progression in breast cancer cells.

Structural insight, mutation and interactions in human Beta-catenin and SOX17 protein: A molecular-level outlook for organogenesis

Essential human proteins; SOX17-HMG domain and beta-catenin uphold a major responsibility for vertebrate gastrulation and embryonic development. Earlier experimental assays document their interaction and states that upon M76A and G103R mutation, their interaction varied. Till date, there was no computational analysis for either of proteins as well as their respective residues for the interaction. The present study extracted and analyzed the experimentally validated 3D models of SOX17-HMG domain and beta-catenin. After analysis of the evolutionarily conserved residues and the sequence-level alteration, the mutated SOX17-HMG protein was re-modeled, demonstrated and energy minimized. Molecular dynamics simulation was performed upon the docked complex of beta-catenin with wild-type and mutant-type protein, individually. Comparable analysis for interaction studies revealed reduction of predominant ionic interactions from 16 (wild-type) to 5 (mutant-type). Glu residues from wild-type protein played a pivotal role forming 50% of the ionic interactions alone. Fascinatingly, statistically significant deductions for several stability calculations deduced the mutant-type protein/complex to form unsteady interaction with beta-catenin. Again, helix-to-coil transition in mutant-type protein supported its weaker conformation. This probe depicts the paramount molecular-level detailed scrutiny for the essential human proteins and disclosure of the mutational analysis, which might tend to hinder the signal transduction. It instigates the future development for the pharmaceutical research.

A Computational Structural Biology of SoxR and DNA: A Modelling and Interactive Discern to Express the Sox Operon in Pseudaminobacter salicylatoxidans (KCT001) for Global Sulphur Oxidation

Computational and microbial molecular-level participation of sox operon and its repressor protein (SoxR) in sulphur oxidation from Pseudaminobacter salicylatoxidans (KCT001) was investigated. Documentation reveals that P. salicylatoxidans (KCT001) has sox TRSVWXYZABCD operon that is regulated by a repressor protein (SoxR). Previously, various experimental procedures such as DMS-mediated DNA methylations and hydroxyl radical footprinting have disclosed that SoxR interacts first with an operator region-sv (present in between soxS and soxV). Detailed computational studies were accomplished in the present study. 3D models of repressor protein and the DNA sequence from operon’s promoter region were demonstrated using molecular modelling techniques. Molecular docking simulation was performed to predict DNA–protein interaction. Amino acid residues and nucleotide bases responsible for interaction were identified by PyMOL and Discovery Studio software suite. This novel residue-level study is paramount for initiating transcription in the operon, thereby leading to sulphur oxidation.

Mutations and interactions in human ERα and bZIP proteins: An in silico approach for cell signaling in breast oncology

I. BACKGROUND Metastasis of breast cancer serves the most aggravating cause for transience in breast cancer patients. Accumulating evidences suggest that signal transduction in human breast cancers commences in estrogen-reliant pattern via signaling of the estrogen-receptor α-subunit (ERα) and XBP-1 (bZIP-domain) proteins. Furthermore, earlier investigations from SAGE and GST pull-down assay, also state that a point mutation in ERα leads to a risky factor by resulting into hyper-responsiveness towards estrogen and increased proliferation of breast cancer cells. So, a molecular-level exploration into the signaling mechanism is a prime requisite for future clinical and therapeutic progress. II. METHODS AND RESULTS Present study explores primarily the residual participation of the two essential proteins from humans to boost the signaling mechanism in malignant breast tumors. So, 3D structures of the respective monomer proteins were demonstrated and mutated protein was homology modeled after the satisfaction of the stereo-chemical features. The functionality was observed to be conserved after mutation. Abrupt increment in protein-protein interactions was studied for the individual optimized and Molecular Dynamics simulated protein complexes. Revelation from supportive statistical significances for several energy calculations, solvent accessibility areas, electrostatic surface potentials and interaction studies led to confer that after mutation, the complex and the individual protein were the most stable and the best interactive one. For metastasis in breast cancer cells, polar charged residues hold a significant contribution. III. CONCLUSION Therefore, this investigation provides a cogent framework for the interactive studies associated with breast cancer and an exposure towards the lethal impact on mutation.

Structural Exploration and Conformational Transitions in MDM2 upon DHFR Interaction from Homo sapiens: A Computational Outlook for Malignancy via Epigenetic Disruption

Structural basis for exploration into MDM2 and MDM2-DHFR interaction plays a vital role in analyzing the obstruction in folate metabolism, nonsynthesis of purines, and further epigenetic regulation in Homo sapiens. Therefore, it leads to suppression of normal cellular behavior and malignancy. This has been earlier documented via yeast two-hybrid assays. So, with a novel outlook, this study explores the molecular level demonstration of the best satisfactory MDM2 model selection after performing manifold modeling techniques. Z-scores and other stereochemical features were estimated for comparison. Further, protein-protein docking was executed with MDM2 and the experimentally validated X-ray crystallographic DHFR. Residual disclosure from the best suited simulated protein complex disclosed 18 side chain and 3 ionic interactions to strongly accommodate MDM2 protein into the pocket-like zone in DHFR due to the positive environment by charged residues. Lysine residues from MDM2 played a predominant role. Moreover, evaluation from varied energy calculations, folding rate, and net area for solvent accessibility implied the active participation of MDM2 with DHFR. Fascinatingly, conformational transitions from coils to helices and β-sheets after interaction with DHFR affirm the conformational strength and firmer interaction of human MDM2-DHFR. Therefore, this probe instigates near-future clinical research and interactive computational investigations with mutations.

Computational structural biology and modes of interaction between human annexin A6 with influenza A virus protein M2: a possible mechanism for reducing viral infection

Influenza-A virus is a prime lethal causative factor for influenza. The M2 protein of influenza A virus plays an important responsibility in the cycle of viral replication. The human Annexin A6 protein targets and stops the viral budding for influenza A virus. Here, molecular level interactions between Annexin A6 and influenza A virus M2 protein were examined. Executing the techniques for molecular modelling, the 3D structures of the two proteins were built via energy optimisations. Interactions between the two proteins were analysed by molecular docking studies. Both Annexin A6 and M2 protein interacted strongly with a pivotal role of Asp and Lys residues, respectively. A conformational shift from helices and sheets to coils was observed in the M2 protein after its interaction with Annexin A6. This probe therefore helped to understand the molecular mechanism of the two proteins and the negative modulation of Annexin A6 on the M2 protein from influenza A virus.

Computational Molecular Analysis of Human Rhodopsin, Transducin and Arrestin Interactions: An Insight into Signal Transduction for Ophthalmology

Retinal G-protein receptor; rhodopsin upon light-activation, gets phosphorylated, experiences conformational shift and interacts with G-protein; transducin. To completely obstruct the signal transduction visual protein; arrestin binds consecutively to disrupt the cationic channels of plasma membrane. Experimented binding assays documents the protein interactions but hitherto computational investigation was undone. This probe aims at the computational study of conformational alterations in rhodopsin upon sequential interactions, accompanied by variations in its surface electrostatic potential and net solvent accessible area. 3D structures of human transducin, arrestin and rhodopsin were analyzed. Residual participation from the optimized and simulated trio-complex (rhodopsin-transducin-arrestin) disclosed that predominantly positively charged amino-acid residues; Arg474, Arg412, Arg229, Arg13, Lys15 and Lys408 from rhodopsin participated with transducin and arrestin forming 9 ionic interactions. Rhodopsin was perceived to interact in a gradual firmer pattern with its partner proteins. This study presents a novel viewpoint into the computational disclosure for participation of concerned visual proteins.

Mutational Impact on the Interaction Between Human IL27 and gp130: In silico Approach for Defending HIV Infection

INTRODUCTION With advances in proteomics, it is essential to investigate the molecularlevel participation of IL27 and gp130 to hinder HIV infection. Their interaction causes cell-cycle arrest in HIV+ cells by activating the receptor-associated JAK signaling and causing apoptosis of cancerous cells. METHODOLOGY The best human wild-type WT_IL27 model was prepared after varied molecular modeling techniques. The vital tyrosine residues in WT_IL27 were identified, mutated and IL27 was re-modeled. Both wild-type and mutant IL27 were docked individually with human gp130 ectodomain complex. Best cluster sized complex was opted and the complexes (WT and MT) were MD (molecular dynamics) simulated. Protein-protein interacting residues, binding patterns, thermodynamic stability, solvent accessibility and many such parameters were evaluated to affirm the stability in the mutant complex. Statistical significances were drawn too. RESULT AND DISCUSSION With statistical significances also, the mutant type (MT) IL27 was comprehended as the most stable one. Their functionality remained the same. Ionic interactions were the most dominating ones. Exceptionally several Arg residues from MT_IL27 appeared to play a major role, thereby stabilizing the simulated MT_IL27-gp130 complexes. Manifold energy estimations for the complexes, electrostatic potential and increment in %helices and %β-sheets revealed the simulated MT_IL27-gp130 complex to be more stable. In the MT_complex, residues forming 3-ten helices remained constant with major increase in α-helices. This thereby infers the complex as the steadiest and most interactive one. CONCLUSION The residual exploration with the detailed structural analysis would aid in the effective drug discovery by targeting the drugs at the interacting sites with the specific binding patterns as analyzed from the study. Conformational stability and other several parameters for thermodynamic stability and accomplishment of strong interaction were also explored. Altogether, this probe provides a limelight towards the mutational alterations in WT IL27, which might allow it to act as a strong peptide inhibitor by shielding HIV entry, more potently.