Debasish Mukherjee | Saha Institute of Nuclear Physics (original) (raw)
Papers by Debasish Mukherjee
Biochimica et Biophysica Acta (BBA) - General Subjects, 2020
Background: Molecular modeling of RNA double helices is possible using most probable values of ba... more Background: Molecular modeling of RNA double helices is possible using most probable values of basepair parameters obtained from crystal structure database. The A:A w:wC non-canonical basepair, involving Watson-Crick edges of two Adenines in cis orientation, appears quite frequently in database. Bimodal distribution of its Shear, due to two different H-bonding schemes, introduces the confusion in assigning most the probable value. Its effect is pronounced when the A:A w:wC basepair stacks on Sheared wobble G:U W:WC basepairs. Methods: We employed molecular dynamics simulations of three possible double helices with GAG, UAG and GAU sequence motifs at their centers and quantum chemical calculation for non-canonical A:A w:wC basepair stacked on G:U W:WC basepair. Results: We noticed stable structures of GAG motif with specifically negative Shear of the A:A basepair but stabilities of the other motifs were not found with A:A w:wC basepairing. Hybrid DFT-D and MP2 stacking energy analyses on dinucleotide step sequences, A:
Journal of molecular modeling, Jan 30, 2017
The structure of a hairpin loop-in particular its large accessible surface area and its exposed h... more The structure of a hairpin loop-in particular its large accessible surface area and its exposed hydrogen-bonding edges-facilitate an inherent possibility for interactions. Just like higher-order RNA macromolecules, pre-microRNAs possess a hairpin loop, and it plays a crucial role in miRNA biogenesis. Upon inspecting the crystal structures of RNAs with various functions, we noticed that, along with a fairly long double helix, the RNAs contained sequentially different hairpin loops comprising four residues. We therefore applied molecular dynamics simulation to analyze six of these previously unexplored tetraloops, along with GNRA (where N is any nucleotide and R is a purine nucleotide) tetraloops, to understand their structural and functional characteristics. A number of analyses quantifying loop stability by examining base-base stacking, base-sugar and base-phosphate hydrogen bonding, and backbone variability were performed. Importantly, we determined the different interbase stacking...
There has been fare amount of debate regarding the contribution of salt-bridges in the stabilizat... more There has been fare amount of debate regarding the contribution of salt-bridges in the stabilization of protein folds. However, their participation in crucial protein functions are well established. The current study analyzes their modes of association, in terms of networks, both within globular proteins and also at protein-protein interfaces. Apart from the most common and trivial case of isolated salt-bridges, bifurcated salt-bridges appear to be a special salt-bridge motif both in terms of its topology and geometry and found ubiquitously in proteins and inter-protein complexes. Interesting and attractive examples presenting different interaction-modes have been highlighted. Bifurcated salt-bridges appear to function as molecular clips instrumental in stitching large surface contours of interacting protein-protein interfaces. The work also emphasizes the key role of salt-bridge mediated interactions in the partial folding of proteins containing large amount of disordered regions. ...
Scientific reports, May 26, 2017
Editing in microRNAs, particularly in seed can significantly alter the choice of their target gen... more Editing in microRNAs, particularly in seed can significantly alter the choice of their target genes. We show that out of 13 different human tissues, different regions of brain showed higher adenosine to inosine (A-to-I) editing in mature miRNAs. These events were enriched in seed sequence (73.33%), which was not observed for cytosine to uracil (17.86%) editing. More than half of the edited miRNAs showed increased stability, 72.7% of which had ΔΔG values less than -6.0 Kcal/mole and for all of them the edited adenosines mis-paired with cytosines on the pre-miRNA structure. A seed-editing event in hsa-miR-411 (with A - C mismatch) lead to increased expression of the mature form compared to the unedited version in cell culture experiments. Further, small RNA sequencing of GBM patients identified significant miRNA hypoediting which correlated with downregulation of ADAR2 both in metadata and qRT-PCR based validation. Twenty-two significant (11 novel) A-to-I hypoediting events were ident...
Journal of computer-aided molecular design, 2017
Comprehensive analyses of structural features of non-canonical base pairs within a nucleic acid d... more Comprehensive analyses of structural features of non-canonical base pairs within a nucleic acid double helix are limited by the availability of a small number of three dimensional structures. Therefore, a procedure for model building of double helices containing any given nucleotide sequence and base pairing information, either canonical or non-canonical, is seriously needed. Here we describe a program RNAHelix, which is an updated version of our widely used software, NUCGEN. The program can regenerate duplexes using the dinucleotide step and base pair orientation parameters for a given double helical DNA or RNA sequence with defined Watson-Crick or non-Watson-Crick base pairs. The original structure and the corresponding regenerated structure of double helices were found to be very close, as indicated by the small RMSD values between positions of the corresponding atoms. Structures of several usual and unusual double helices have been regenerated and compared with their original st...
Research in Microbiology, 2014
A Gram-negative, short rod, aerobic bacterium, designated W11 T , was isolated from seawater. Het... more A Gram-negative, short rod, aerobic bacterium, designated W11 T , was isolated from seawater. Heterotrophic growth was observed at 10e45 C and pH 6e10. Optimal growth was observed at 30e37 C and pH 7e9. It can grow in the presence of 0.5e12% NaCl (w/v), and the optimal NaCl required for growth was 5e6%. 16S rRNA gene sequence similarity revealed that strain W11 T clustered within the radiation of the genus Idiomarina and showed 99.24% similarity with Idiomarina donghaiensis JCM 15533 T , 97.64% with Idiomarina marina JCM 15083 T , 97.37% with Idiomarina tainanensis JCM 15084 T and 97.16% with Idiomarina maritima JCM 15534 T. DNAeDNA similarities between strains W11 T with other closely related strains were below 70%. Polar lipids included a phosphatidylgylycerol, a diphosphatidylglycerol, a phosphatidylethanolamine, an unidentified phosopholipid, two unidentified aminolipids and two unidentified lipids. DNA G þ C content was 41.2 ± 0.1 mol%. Major fatty acids were iso-C 15:0 , iso-C 17:0 , iso-C 17:1 u9c, C 16:0 , iso-C 11:0 3OH and C 16:1 u7c/C 16:1 u7c. The isoprenoid ubiquinone was Q8. On the basis of the present polyphasic taxonomic study, strain W11 T is considered to represent a novel species of the genus Idiomarina, for which the name Idiomarina woesei sp. nov.
Interdisciplinary Sciences: Computational Life Sciences
Journal of Computer-Aided Molecular Design, 2017
structures in terms of base pair RMSD, torsion angles and electrostatic potentials and very high ... more structures in terms of base pair RMSD, torsion angles and electrostatic potentials and very high agreements have been noted. RNAHelix can also be used to generate a structure with a sequence completely different from an experimentally determined one or to introduce single to multiple mutation, but with the same set of parameters and hence can also be an important tool in homology modeling and study of mutation induced structural changes. Keywords Molecular modeling · RNA · Non Watson– Crick base pairs · Base pair parameters · Dinucleotide step parameters · Electrostatic potential
Journal of Molecular Modeling, 2017
There has been considerable debate about the contribution of salt bridges to the stabilization of... more There has been considerable debate about the contribution of salt bridges to the stabilization of protein folds, in spite of their participation in crucial protein functions. Salt bridges appear to contribute to the activity–stability trade-off within proteins by bringing high-entropy charged amino acids into close contacts during the course of their functions. The current study analyzes the modes of association of salt bridges (in terms of networks) within globular proteins and at protein– protein interfaces. While the most common and trivial type of salt bridge is the isolated salt bridge, bifurcated salt bridge appears to be a distinct salt-bridge motif having a special topology and geometry. Bifurcated salt bridges are found ubiquitously in proteins and interprotein complexes. Interesting and attractive examples presenting different modes of interaction are highlighted. Bifurcated salt bridges appear to function as molecular clips that are used to stitch together large surface contours at interacting protein interfaces. The present work also emphasizes the key role of salt-bridge-mediated interactions in the partial folding of proteins containing long stretches of disordered regions. Salt-bridge-mediated interactions seem to be pivotal to the promotion of Bdisorder-to-order^ transitions in small disordered protein fragments and their stabilization upon binding. The results obtained in this work should help to guide efforts to elucidate the modus operandi of these partially disordered proteins, and to conceptualize how these proteins manage to maintain the required amount of disorder even in their bound forms. This work could also potentially facilitate explorations of geometrically specific designable salt bridges through the characterization of composite salt-bridge networks.
There has been considerable debate about the contribution of salt bridges to the stabilization of... more There has been considerable debate about the contribution of salt bridges to the stabilization of protein folds, in spite of their participation in crucial protein functions. Salt bridges appear to contribute to the activity–stability trade-off within proteins by bringing high-entropy charged amino acids into close contacts during the course of their functions. The current study analyzes the modes of association of salt bridges (in terms of networks) within globular proteins and at protein– protein interfaces. While the most common and trivial type of salt bridge is the isolated salt bridge, bifurcated salt bridge appears to be a distinct salt-bridge motif having a special topology and geometry. Bifurcated salt bridges are found ubiquitously in proteins and interprotein complexes. Interesting and attractive examples presenting different modes of interaction are highlighted. Bifurcated salt bridges appear to function as molecular clips that are used to stitch together large surface contours at interacting protein interfaces. The present work also emphasizes the key role of salt-bridge-mediated interactions in the partial folding of proteins containing long stretches of disordered regions. Salt-bridge-mediated interactions seem to be pivotal to the promotion of Bdisorder-to-order^ transitions in small disordered protein fragments and their stabilization upon binding. The results obtained in this work should help to guide efforts to elucidate the modus operandi of these partially disordered proteins, and to conceptualize how these proteins manage to maintain the required amount of disorder even in their bound forms. This work could also potentially facilitate explorations of geometrically specific designable salt bridges through the characterization of composite salt-bridge networks.
Editing in microRNAs, particularly in seed can significantly alter the choice of their target gen... more Editing in microRNAs, particularly in seed can significantly alter the choice of their target genes. We show that out of 13 different human tissues, different regions of brain showed higher adenosine to inosine (A-to-I) editing in mature miRNAs. These events were enriched in seed sequence (73.33%), which was not observed for cytosine to uracil (17.86%) editing. More than half of the edited miRNAs showed increased stability, 72.7% of which had ΔΔG values less than −6.0 Kcal/mole and for all of them the edited adenosines mis-paired with cytosines on the pre-miRNA structure. A seed-editing event in hsa-miR-411 (with A – C mismatch) lead to increased expression of the mature form compared to the unedited version in cell culture experiments. Further, small RNA sequencing of GBM patients identified significant miRNA hypoediting which correlated with downregulation of ADAR2 both in metadata and qRT-PCR based validation. Twenty-two significant (11 novel) A-to-I hypoediting events were identified in GBM samples. This study highlights the importance of specific sequence and structural requirements of pre-miRNA for editing along with a suggestive crucial role for ADAR2. Enrichment of A-to-I editing in seed sequence highlights this as an important layer for genomic regulation in health and disease, especially in human brain. RNA molecules undergo multiple post-transcriptional modifications 1 for performing diverse functions. Various efforts have been made for identification 2, 3 and understanding the significance of these modifications 4, 5. RNA editing – the most well studied modification-changes the information encoded by the genome and adds complexity to the gene regulatory networks 6–8. The predominant editing event, adenosine-to-inosine (A-to-I) is mediated by ADAR (Adenosine deaminase acting on RNA) family members which acts on double-stranded RNA (dsRNA) with or without a perfect complementarity 9. With the advent of next generation sequencing multiple groups have devised experimental 10, 11 as well as computational 12, 13 approaches to identify genome-wide A-to-I editing events in RNA. For protein-coding transcripts A-to-I editing is essential for normal development 14, 15 and is enriched in the brain 16. A-to-I modification happens more promiscuously within perfect dsRNA substrates, deaminating up to 50% of the adenosine residues 17 whereas internal mismatches and bulges in dsRNA substrates is associated with ADAR selectivity 18. Another form of canonical RNA editing event involves cytosine to uracil (C-to-U) deamination 15 mediated by APOBEC1 (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 1). APOBEC1 mediated editing events provide tissue specificity and diversity for ApoB mRNAs 19 but deregulation of APOBEC1 can also bring about devastating phenotype like cancer 20 .
structures in terms of base pair RMSD, torsion angles and electrostatic potentials and very high ... more structures in terms of base pair RMSD, torsion angles and electrostatic potentials and very high agreements have been noted. RNAHelix can also be used to generate a structure with a sequence completely different from an experimentally determined one or to introduce single to multiple mutation, but with the same set of parameters and hence can also be an important tool in homology modeling and study of mutation induced structural changes. Keywords Molecular modeling · RNA · Non Watson– Crick base pairs · Base pair parameters · Dinucleotide step parameters · Electrostatic potential
A Gram-negative, short rod, aerobic bacterium, designated W11 T , was isolated from seawater. Het... more A Gram-negative, short rod, aerobic bacterium, designated W11 T , was isolated from seawater. Heterotrophic growth was observed at 10e45 C and pH 6e10. Optimal growth was observed at 30e37 C and pH 7e9. It can grow in the presence of 0.5e12% NaCl (w/v), and the optimal NaCl required for growth was 5e6%. 16S rRNA gene sequence similarity revealed that strain W11 T clustered within the radiation of the genus Idiomarina and showed 99.24% similarity with Idiomarina donghaiensis JCM 15533 T , 97.64% with Idiomarina marina JCM 15083 T , 97.37% with Idiomarina tainanensis JCM 15084 T and 97.16% with Idiomarina maritima JCM 15534 T. DNAeDNA similarities between strains W11 T with other closely related strains were below 70%. Polar lipids included a phosphatidylgylycerol, a diphosphatidylglycerol, a phos-phatidylethanolamine, an unidentified phosopholipid, two unidentified aminolipids and two unidentified lipids. DNA G þ C content was 41.2 ± 0.1 mol%. Major fatty acids were iso-C 15:0 , iso-C 17:0 , iso-C 17:1 u9c, C 16:0 , iso-C 11:0 3OH and C 16:1 u7c/C 16:1 u7c. The isoprenoid ubiquinone was Q8. On the basis of the present polyphasic taxonomic study, strain W11 T is considered to represent a novel species of the genus Idiomarina, for which the name Idiomarina woesei sp. nov. is proposed. The type strain is W11 T (¼ DSM 27808 T ¼ JCM 19499 T ¼ LMG 27903 T).
Journal of computer-aided molecular design, 2014
RNA contains different secondary structural motifs like pseudo-helices, hairpin loops, internal l... more RNA contains different secondary structural motifs like pseudo-helices, hairpin loops, internal loops, etc. in addition to anti-parallel double helices and random coils. The secondary structures are mainly stabilized by base-pairing and stacking interactions between the planar aromatic bases. The hydrogen bonding strength and geometries of base pairs are characterized by six intra-base pair parameters. Similarly, stacking can be represented by six local doublet parameters. These dinucleotide step parameters can describe the quality of stacking between Watson–Crick base pairs very effectively. However, it is quite difficult to understand the stacking pattern for dinucleotides consisting of non canonical base pairs from these parameters. Stacking interaction is a manifestation of the interaction between two aromatic bases or base pairs and thus can be estimated best by the overlap area between the planar aromatic moieties. We have calculated base pair overlap between two consecutive base pairs as the buried van der Waals surface between them. In general, overlap values show normal distribution for the Watson–Crick base pairs in most double helices within a range from 45 to 50 Å2 irrespective of base sequence. The dinucleotide steps with non-canonical base pairs also are seen to have high overlap value, although their twist and few other parameters are rather unusual. We have analyzed hairpin loops of different length, bulges within double helical structures and pseudo-continuous helices using our algorithm. The overlap area analyses indicate good stacking between few looped out bases especially in GNRA tetraloop, which was difficult to quantitatively characterise from analysis of the base pair or dinucleotide step parameters. This parameter is also seen to be capable to distinguish pseudo-continuous helices from kinked helix junctions.
Biochimica et Biophysica Acta (BBA) - General Subjects, 2020
Background: Molecular modeling of RNA double helices is possible using most probable values of ba... more Background: Molecular modeling of RNA double helices is possible using most probable values of basepair parameters obtained from crystal structure database. The A:A w:wC non-canonical basepair, involving Watson-Crick edges of two Adenines in cis orientation, appears quite frequently in database. Bimodal distribution of its Shear, due to two different H-bonding schemes, introduces the confusion in assigning most the probable value. Its effect is pronounced when the A:A w:wC basepair stacks on Sheared wobble G:U W:WC basepairs. Methods: We employed molecular dynamics simulations of three possible double helices with GAG, UAG and GAU sequence motifs at their centers and quantum chemical calculation for non-canonical A:A w:wC basepair stacked on G:U W:WC basepair. Results: We noticed stable structures of GAG motif with specifically negative Shear of the A:A basepair but stabilities of the other motifs were not found with A:A w:wC basepairing. Hybrid DFT-D and MP2 stacking energy analyses on dinucleotide step sequences, A:
Journal of molecular modeling, Jan 30, 2017
The structure of a hairpin loop-in particular its large accessible surface area and its exposed h... more The structure of a hairpin loop-in particular its large accessible surface area and its exposed hydrogen-bonding edges-facilitate an inherent possibility for interactions. Just like higher-order RNA macromolecules, pre-microRNAs possess a hairpin loop, and it plays a crucial role in miRNA biogenesis. Upon inspecting the crystal structures of RNAs with various functions, we noticed that, along with a fairly long double helix, the RNAs contained sequentially different hairpin loops comprising four residues. We therefore applied molecular dynamics simulation to analyze six of these previously unexplored tetraloops, along with GNRA (where N is any nucleotide and R is a purine nucleotide) tetraloops, to understand their structural and functional characteristics. A number of analyses quantifying loop stability by examining base-base stacking, base-sugar and base-phosphate hydrogen bonding, and backbone variability were performed. Importantly, we determined the different interbase stacking...
There has been fare amount of debate regarding the contribution of salt-bridges in the stabilizat... more There has been fare amount of debate regarding the contribution of salt-bridges in the stabilization of protein folds. However, their participation in crucial protein functions are well established. The current study analyzes their modes of association, in terms of networks, both within globular proteins and also at protein-protein interfaces. Apart from the most common and trivial case of isolated salt-bridges, bifurcated salt-bridges appear to be a special salt-bridge motif both in terms of its topology and geometry and found ubiquitously in proteins and inter-protein complexes. Interesting and attractive examples presenting different interaction-modes have been highlighted. Bifurcated salt-bridges appear to function as molecular clips instrumental in stitching large surface contours of interacting protein-protein interfaces. The work also emphasizes the key role of salt-bridge mediated interactions in the partial folding of proteins containing large amount of disordered regions. ...
Scientific reports, May 26, 2017
Editing in microRNAs, particularly in seed can significantly alter the choice of their target gen... more Editing in microRNAs, particularly in seed can significantly alter the choice of their target genes. We show that out of 13 different human tissues, different regions of brain showed higher adenosine to inosine (A-to-I) editing in mature miRNAs. These events were enriched in seed sequence (73.33%), which was not observed for cytosine to uracil (17.86%) editing. More than half of the edited miRNAs showed increased stability, 72.7% of which had ΔΔG values less than -6.0 Kcal/mole and for all of them the edited adenosines mis-paired with cytosines on the pre-miRNA structure. A seed-editing event in hsa-miR-411 (with A - C mismatch) lead to increased expression of the mature form compared to the unedited version in cell culture experiments. Further, small RNA sequencing of GBM patients identified significant miRNA hypoediting which correlated with downregulation of ADAR2 both in metadata and qRT-PCR based validation. Twenty-two significant (11 novel) A-to-I hypoediting events were ident...
Journal of computer-aided molecular design, 2017
Comprehensive analyses of structural features of non-canonical base pairs within a nucleic acid d... more Comprehensive analyses of structural features of non-canonical base pairs within a nucleic acid double helix are limited by the availability of a small number of three dimensional structures. Therefore, a procedure for model building of double helices containing any given nucleotide sequence and base pairing information, either canonical or non-canonical, is seriously needed. Here we describe a program RNAHelix, which is an updated version of our widely used software, NUCGEN. The program can regenerate duplexes using the dinucleotide step and base pair orientation parameters for a given double helical DNA or RNA sequence with defined Watson-Crick or non-Watson-Crick base pairs. The original structure and the corresponding regenerated structure of double helices were found to be very close, as indicated by the small RMSD values between positions of the corresponding atoms. Structures of several usual and unusual double helices have been regenerated and compared with their original st...
Research in Microbiology, 2014
A Gram-negative, short rod, aerobic bacterium, designated W11 T , was isolated from seawater. Het... more A Gram-negative, short rod, aerobic bacterium, designated W11 T , was isolated from seawater. Heterotrophic growth was observed at 10e45 C and pH 6e10. Optimal growth was observed at 30e37 C and pH 7e9. It can grow in the presence of 0.5e12% NaCl (w/v), and the optimal NaCl required for growth was 5e6%. 16S rRNA gene sequence similarity revealed that strain W11 T clustered within the radiation of the genus Idiomarina and showed 99.24% similarity with Idiomarina donghaiensis JCM 15533 T , 97.64% with Idiomarina marina JCM 15083 T , 97.37% with Idiomarina tainanensis JCM 15084 T and 97.16% with Idiomarina maritima JCM 15534 T. DNAeDNA similarities between strains W11 T with other closely related strains were below 70%. Polar lipids included a phosphatidylgylycerol, a diphosphatidylglycerol, a phosphatidylethanolamine, an unidentified phosopholipid, two unidentified aminolipids and two unidentified lipids. DNA G þ C content was 41.2 ± 0.1 mol%. Major fatty acids were iso-C 15:0 , iso-C 17:0 , iso-C 17:1 u9c, C 16:0 , iso-C 11:0 3OH and C 16:1 u7c/C 16:1 u7c. The isoprenoid ubiquinone was Q8. On the basis of the present polyphasic taxonomic study, strain W11 T is considered to represent a novel species of the genus Idiomarina, for which the name Idiomarina woesei sp. nov.
Interdisciplinary Sciences: Computational Life Sciences
Journal of Computer-Aided Molecular Design, 2017
structures in terms of base pair RMSD, torsion angles and electrostatic potentials and very high ... more structures in terms of base pair RMSD, torsion angles and electrostatic potentials and very high agreements have been noted. RNAHelix can also be used to generate a structure with a sequence completely different from an experimentally determined one or to introduce single to multiple mutation, but with the same set of parameters and hence can also be an important tool in homology modeling and study of mutation induced structural changes. Keywords Molecular modeling · RNA · Non Watson– Crick base pairs · Base pair parameters · Dinucleotide step parameters · Electrostatic potential
Journal of Molecular Modeling, 2017
There has been considerable debate about the contribution of salt bridges to the stabilization of... more There has been considerable debate about the contribution of salt bridges to the stabilization of protein folds, in spite of their participation in crucial protein functions. Salt bridges appear to contribute to the activity–stability trade-off within proteins by bringing high-entropy charged amino acids into close contacts during the course of their functions. The current study analyzes the modes of association of salt bridges (in terms of networks) within globular proteins and at protein– protein interfaces. While the most common and trivial type of salt bridge is the isolated salt bridge, bifurcated salt bridge appears to be a distinct salt-bridge motif having a special topology and geometry. Bifurcated salt bridges are found ubiquitously in proteins and interprotein complexes. Interesting and attractive examples presenting different modes of interaction are highlighted. Bifurcated salt bridges appear to function as molecular clips that are used to stitch together large surface contours at interacting protein interfaces. The present work also emphasizes the key role of salt-bridge-mediated interactions in the partial folding of proteins containing long stretches of disordered regions. Salt-bridge-mediated interactions seem to be pivotal to the promotion of Bdisorder-to-order^ transitions in small disordered protein fragments and their stabilization upon binding. The results obtained in this work should help to guide efforts to elucidate the modus operandi of these partially disordered proteins, and to conceptualize how these proteins manage to maintain the required amount of disorder even in their bound forms. This work could also potentially facilitate explorations of geometrically specific designable salt bridges through the characterization of composite salt-bridge networks.
There has been considerable debate about the contribution of salt bridges to the stabilization of... more There has been considerable debate about the contribution of salt bridges to the stabilization of protein folds, in spite of their participation in crucial protein functions. Salt bridges appear to contribute to the activity–stability trade-off within proteins by bringing high-entropy charged amino acids into close contacts during the course of their functions. The current study analyzes the modes of association of salt bridges (in terms of networks) within globular proteins and at protein– protein interfaces. While the most common and trivial type of salt bridge is the isolated salt bridge, bifurcated salt bridge appears to be a distinct salt-bridge motif having a special topology and geometry. Bifurcated salt bridges are found ubiquitously in proteins and interprotein complexes. Interesting and attractive examples presenting different modes of interaction are highlighted. Bifurcated salt bridges appear to function as molecular clips that are used to stitch together large surface contours at interacting protein interfaces. The present work also emphasizes the key role of salt-bridge-mediated interactions in the partial folding of proteins containing long stretches of disordered regions. Salt-bridge-mediated interactions seem to be pivotal to the promotion of Bdisorder-to-order^ transitions in small disordered protein fragments and their stabilization upon binding. The results obtained in this work should help to guide efforts to elucidate the modus operandi of these partially disordered proteins, and to conceptualize how these proteins manage to maintain the required amount of disorder even in their bound forms. This work could also potentially facilitate explorations of geometrically specific designable salt bridges through the characterization of composite salt-bridge networks.
Editing in microRNAs, particularly in seed can significantly alter the choice of their target gen... more Editing in microRNAs, particularly in seed can significantly alter the choice of their target genes. We show that out of 13 different human tissues, different regions of brain showed higher adenosine to inosine (A-to-I) editing in mature miRNAs. These events were enriched in seed sequence (73.33%), which was not observed for cytosine to uracil (17.86%) editing. More than half of the edited miRNAs showed increased stability, 72.7% of which had ΔΔG values less than −6.0 Kcal/mole and for all of them the edited adenosines mis-paired with cytosines on the pre-miRNA structure. A seed-editing event in hsa-miR-411 (with A – C mismatch) lead to increased expression of the mature form compared to the unedited version in cell culture experiments. Further, small RNA sequencing of GBM patients identified significant miRNA hypoediting which correlated with downregulation of ADAR2 both in metadata and qRT-PCR based validation. Twenty-two significant (11 novel) A-to-I hypoediting events were identified in GBM samples. This study highlights the importance of specific sequence and structural requirements of pre-miRNA for editing along with a suggestive crucial role for ADAR2. Enrichment of A-to-I editing in seed sequence highlights this as an important layer for genomic regulation in health and disease, especially in human brain. RNA molecules undergo multiple post-transcriptional modifications 1 for performing diverse functions. Various efforts have been made for identification 2, 3 and understanding the significance of these modifications 4, 5. RNA editing – the most well studied modification-changes the information encoded by the genome and adds complexity to the gene regulatory networks 6–8. The predominant editing event, adenosine-to-inosine (A-to-I) is mediated by ADAR (Adenosine deaminase acting on RNA) family members which acts on double-stranded RNA (dsRNA) with or without a perfect complementarity 9. With the advent of next generation sequencing multiple groups have devised experimental 10, 11 as well as computational 12, 13 approaches to identify genome-wide A-to-I editing events in RNA. For protein-coding transcripts A-to-I editing is essential for normal development 14, 15 and is enriched in the brain 16. A-to-I modification happens more promiscuously within perfect dsRNA substrates, deaminating up to 50% of the adenosine residues 17 whereas internal mismatches and bulges in dsRNA substrates is associated with ADAR selectivity 18. Another form of canonical RNA editing event involves cytosine to uracil (C-to-U) deamination 15 mediated by APOBEC1 (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 1). APOBEC1 mediated editing events provide tissue specificity and diversity for ApoB mRNAs 19 but deregulation of APOBEC1 can also bring about devastating phenotype like cancer 20 .
structures in terms of base pair RMSD, torsion angles and electrostatic potentials and very high ... more structures in terms of base pair RMSD, torsion angles and electrostatic potentials and very high agreements have been noted. RNAHelix can also be used to generate a structure with a sequence completely different from an experimentally determined one or to introduce single to multiple mutation, but with the same set of parameters and hence can also be an important tool in homology modeling and study of mutation induced structural changes. Keywords Molecular modeling · RNA · Non Watson– Crick base pairs · Base pair parameters · Dinucleotide step parameters · Electrostatic potential
A Gram-negative, short rod, aerobic bacterium, designated W11 T , was isolated from seawater. Het... more A Gram-negative, short rod, aerobic bacterium, designated W11 T , was isolated from seawater. Heterotrophic growth was observed at 10e45 C and pH 6e10. Optimal growth was observed at 30e37 C and pH 7e9. It can grow in the presence of 0.5e12% NaCl (w/v), and the optimal NaCl required for growth was 5e6%. 16S rRNA gene sequence similarity revealed that strain W11 T clustered within the radiation of the genus Idiomarina and showed 99.24% similarity with Idiomarina donghaiensis JCM 15533 T , 97.64% with Idiomarina marina JCM 15083 T , 97.37% with Idiomarina tainanensis JCM 15084 T and 97.16% with Idiomarina maritima JCM 15534 T. DNAeDNA similarities between strains W11 T with other closely related strains were below 70%. Polar lipids included a phosphatidylgylycerol, a diphosphatidylglycerol, a phos-phatidylethanolamine, an unidentified phosopholipid, two unidentified aminolipids and two unidentified lipids. DNA G þ C content was 41.2 ± 0.1 mol%. Major fatty acids were iso-C 15:0 , iso-C 17:0 , iso-C 17:1 u9c, C 16:0 , iso-C 11:0 3OH and C 16:1 u7c/C 16:1 u7c. The isoprenoid ubiquinone was Q8. On the basis of the present polyphasic taxonomic study, strain W11 T is considered to represent a novel species of the genus Idiomarina, for which the name Idiomarina woesei sp. nov. is proposed. The type strain is W11 T (¼ DSM 27808 T ¼ JCM 19499 T ¼ LMG 27903 T).
Journal of computer-aided molecular design, 2014
RNA contains different secondary structural motifs like pseudo-helices, hairpin loops, internal l... more RNA contains different secondary structural motifs like pseudo-helices, hairpin loops, internal loops, etc. in addition to anti-parallel double helices and random coils. The secondary structures are mainly stabilized by base-pairing and stacking interactions between the planar aromatic bases. The hydrogen bonding strength and geometries of base pairs are characterized by six intra-base pair parameters. Similarly, stacking can be represented by six local doublet parameters. These dinucleotide step parameters can describe the quality of stacking between Watson–Crick base pairs very effectively. However, it is quite difficult to understand the stacking pattern for dinucleotides consisting of non canonical base pairs from these parameters. Stacking interaction is a manifestation of the interaction between two aromatic bases or base pairs and thus can be estimated best by the overlap area between the planar aromatic moieties. We have calculated base pair overlap between two consecutive base pairs as the buried van der Waals surface between them. In general, overlap values show normal distribution for the Watson–Crick base pairs in most double helices within a range from 45 to 50 Å2 irrespective of base sequence. The dinucleotide steps with non-canonical base pairs also are seen to have high overlap value, although their twist and few other parameters are rather unusual. We have analyzed hairpin loops of different length, bulges within double helical structures and pseudo-continuous helices using our algorithm. The overlap area analyses indicate good stacking between few looped out bases especially in GNRA tetraloop, which was difficult to quantitatively characterise from analysis of the base pair or dinucleotide step parameters. This parameter is also seen to be capable to distinguish pseudo-continuous helices from kinked helix junctions.