cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.825496
title: Video observation of surface exploration in cyprids of <i>Balanus amphitrite</i>: the movements of antennular sensory setae

description: Video microscopy of cyprids of <i>Balanus amphitrite</i> was used to monitor the action of antennular setae during the exploratory behaviour prior to attachment. In addition, SEM was used to provide a revised description of all antennular setae for that species. The videos describe if a particular seta touches the substratum and the area it can cover during surface exploration. On the fourth segment, the plumose terminal setae A and B are never in contact with the substratum, lack a terminal pore and it is argued that they sense hydrodynamic forces. The aesthetasc-like terminal seta D is likewise held free in the water at all times and it is speculated that it senses dissolved substances, but, since it contains a scolopale rod, it must also have a mechano-receptive function. All remaining antennular setae on the second, third and fourth segments have a terminal pore and it is argued that these are bimodal receptors with both chemo- and mechano-receptive modalities. These setae are also at one time or another in contact with the substratum, except perhaps for the small preaxial seta 2 and terminal seta C. The first seta to contact the surface during a tentative step is radial seta 5, which is longer than all other radial setae. All other setae on the second and third segment are only in contact after a step is completed. When the attachment disc touches the surface (=a step completed) the long and curved postaxial seta 2 (on the second segment) and postaxial seta 3 on the third segment are both flexed to either side of the antennule. This lateral displacement ensures that these two setae can touch large surface areas to either side of the appendage. The four subterminal setae on the fourth segment contact the surface both immediately before and after a step has been completed, and the constant flicking of the segment significantly increases the surface area tested by both these chemoreceptors and by terminal seta E, which can sweep up to 60 μm laterally from the attachment disc. The flicking of the fourth segment may also serve to dilute the boundary layer of chemoreceptors on the fourth segment such as the aesthetasc-like terminal seta D and thus facilitate the detection of new stimuli.
DOI: 10.6084/m9.figshare.825494
title: Structure prediction of gBP21 protein of <i>L. donovani</i> and its molecular interaction

description: Visceral leishmaniasis (Kala-azar) is a fatal disease caused by the obligate intracellular parasite <i>Leishmania donovani</i> and the available drugs for the treatment are few, and are frequently associated with side effects and toxicity. RNA editing is one of the essential metabolic processes in the kinetoplastids, where the pre-mRNAs are edited post-transcriptionally by the guide RNAs with the addition or deletion of uridine residues. The aim is to block the gBP21 protein involved in RNA editing process thereby other direct and indirect protein activity is reduced and ultimately the editing process in <i>L. donovani</i> is disturbed and it will inhibit the growth. RNA editing factors are RNA-linked proteins essential for <i>in vivo</i> editing i.e. mitochondrial RNA binding protein1 (MRP 1) originally called as gBP21. The model of <i>L. donovani</i> gBP21 (gBP21Ldv) showed that this protein bears an anti-parallel ß sheet (segregated α and ß regions) with ß-ß-ß-ß-α-ß-ß-ß-ß-α-type topology (“whirly” transcription-factor fold). Each of the four ß strands within a given ß-ß-ß-ß-α repeats and form a curved anti-parallel ß-sheet that packs perpendicularly against the sheet from the other repeat. Among all of the computationally screened compounds by the GLIDE program (Schrödinger) and GOLD program hyperoside1a, posaconazole, quercetin, and pentanediol, 427 exhibited higher binding affinities with the modeled gBP21 protein of <i>L. donovani</i>. Ligandfit program <i>(</i>DSv2.5) revealed that DNA, RNA polymerase inhibitors acyclovir, mitomycin C, and daunorubicin have better binding affinity towards gBP21Ldv. These compounds may be given in combination with miltefosine (first line therapy) against patients with VL and other associated disorders like anemia.
DOI: 10.6084/m9.figshare.825496.v1
title: Video observation of surface exploration in cyprids of <i>Balanus amphitrite</i>: the movements of antennular sensory setae

description: Video microscopy of cyprids of <i>Balanus amphitrite</i> was used to monitor the action of antennular setae during the exploratory behaviour prior to attachment. In addition, SEM was used to provide a revised description of all antennular setae for that species. The videos describe if a particular seta touches the substratum and the area it can cover during surface exploration. On the fourth segment, the plumose terminal setae A and B are never in contact with the substratum, lack a terminal pore and it is argued that they sense hydrodynamic forces. The aesthetasc-like terminal seta D is likewise held free in the water at all times and it is speculated that it senses dissolved substances, but, since it contains a scolopale rod, it must also have a mechano-receptive function. All remaining antennular setae on the second, third and fourth segments have a terminal pore and it is argued that these are bimodal receptors with both chemo- and mechano-receptive modalities. These setae are also at one time or another in contact with the substratum, except perhaps for the small preaxial seta 2 and terminal seta C. The first seta to contact the surface during a tentative step is radial seta 5, which is longer than all other radial setae. All other setae on the second and third segment are only in contact after a step is completed. When the attachment disc touches the surface (=a step completed) the long and curved postaxial seta 2 (on the second segment) and postaxial seta 3 on the third segment are both flexed to either side of the antennule. This lateral displacement ensures that these two setae can touch large surface areas to either side of the appendage. The four subterminal setae on the fourth segment contact the surface both immediately before and after a step has been completed, and the constant flicking of the segment significantly increases the surface area tested by both these chemoreceptors and by terminal seta E, which can sweep up to 60 μm laterally from the attachment disc. The flicking of the fourth segment may also serve to dilute the boundary layer of chemoreceptors on the fourth segment such as the aesthetasc-like terminal seta D and thus facilitate the detection of new stimuli.
DOI: 10.6084/m9.figshare.825493
title: Membrane undulation induced by NS4A of Dengue virus: a molecular dynamics simulation study

description: Nonstructural protein 4A (NS4A) of Dengue virus (DENV) is a membrane protein involved in rearrangements of the endoplasmic reticulum membrane that are required for formation of replication vesicles. NS4A is composed most likely of three membrane domains. The N- and C-terminal domains are supposed to traverse the lipid membrane whereas the central one is thought to reside on the membrane surface, thus forming a <i>u</i>-shaped protein. All three membrane domains are proposed to be helical by secondary structure prediction programs. After performing multi nanosecond molecular dynamics (MD) simulations at various temperatures (300, 310, and 315.15 K) with each of the individual domains, they are used in a docking approach to define putative association motifs of the transmembrane domains (TMDs). Two structures of the <i>u</i>-shaped protein are generated by separating two assembled TMDs linking them with the membrane-attached domain. Lipid undulation is monitored with the structures embedded in a fully hydrated lipid bilayer applying multiple 200 ns MD simulations at 310 K. An intact structure of the protein supports membrane undulation. The strong unwinding of the helices in the domain-linking section of one of the structures lowers its capability to induce membrane curvature. Unwinding of the link region is due to interactions of two tryptophan residues, Trp-96 and 104. These results provide first insights into the membrane-altering properties of DENV NS4A.
DOI: 10.6084/m9.figshare.825494.v2
title: Structure prediction of gBP21 protein of <i>L. donovani</i> and its molecular interaction

description: Visceral leishmaniasis (Kala-azar) is a fatal disease caused by the obligate intracellular parasite <i>Leishmania donovani</i> and the available drugs for the treatment are few, and are frequently associated with side effects and toxicity. RNA editing is one of the essential metabolic processes in the kinetoplastids, where the pre-mRNAs are edited post-transcriptionally by the guide RNAs with the addition or deletion of uridine residues. The aim is to block the gBP21 protein involved in RNA editing process thereby other direct and indirect protein activity is reduced and ultimately the editing process in <i>L. donovani</i> is disturbed and it will inhibit the growth. RNA editing factors are RNA-linked proteins essential for <i>in vivo</i> editing i.e. mitochondrial RNA binding protein1 (MRP 1) originally called as gBP21. The model of <i>L. donovani</i> gBP21 (gBP21Ldv) showed that this protein bears an anti-parallel ß sheet (segregated α and ß regions) with ß-ß-ß-ß-α-ß-ß-ß-ß-α-type topology (“whirly” transcription-factor fold). Each of the four ß strands within a given ß-ß-ß-ß-α repeats and form a curved anti-parallel ß-sheet that packs perpendicularly against the sheet from the other repeat. Among all of the computationally screened compounds by the GLIDE program (Schrödinger) and GOLD program hyperoside1a, posaconazole, quercetin, and pentanediol, 427 exhibited higher binding affinities with the modeled gBP21 protein of <i>L. donovani</i>. Ligandfit program <i>(</i>DSv2.5) revealed that DNA, RNA polymerase inhibitors acyclovir, mitomycin C, and daunorubicin have better binding affinity towards gBP21Ldv. These compounds may be given in combination with miltefosine (first line therapy) against patients with VL and other associated disorders like anemia.
DOI: 10.6084/m9.figshare.825493.v2
title: Membrane undulation induced by NS4A of Dengue virus: a molecular dynamics simulation study

description: Nonstructural protein 4A (NS4A) of Dengue virus (DENV) is a membrane protein involved in rearrangements of the endoplasmic reticulum membrane that are required for formation of replication vesicles. NS4A is composed most likely of three membrane domains. The N- and C-terminal domains are supposed to traverse the lipid membrane whereas the central one is thought to reside on the membrane surface, thus forming a <i>u</i>-shaped protein. All three membrane domains are proposed to be helical by secondary structure prediction programs. After performing multi nanosecond molecular dynamics (MD) simulations at various temperatures (300, 310, and 315.15 K) with each of the individual domains, they are used in a docking approach to define putative association motifs of the transmembrane domains (TMDs). Two structures of the <i>u</i>-shaped protein are generated by separating two assembled TMDs linking them with the membrane-attached domain. Lipid undulation is monitored with the structures embedded in a fully hydrated lipid bilayer applying multiple 200 ns MD simulations at 310 K. An intact structure of the protein supports membrane undulation. The strong unwinding of the helices in the domain-linking section of one of the structures lowers its capability to induce membrane curvature. Unwinding of the link region is due to interactions of two tryptophan residues, Trp-96 and 104. These results provide first insights into the membrane-altering properties of DENV NS4A.
DOI: 10.6084/m9.figshare.825494.v1
title: Structure prediction of gBP21 protein of <i>L. donovani</i> and its molecular interaction

description: Visceral leishmaniasis (Kala-azar) is a fatal disease caused by the obligate intracellular parasite <i>Leishmania donovani</i> and the available drugs for the treatment are few, and are frequently associated with side effects and toxicity. RNA editing is one of the essential metabolic processes in the kinetoplastids, where the pre-mRNAs are edited post-transcriptionally by the guide RNAs with the addition or deletion of uridine residues. The aim is to block the gBP21 protein involved in RNA editing process thereby other direct and indirect protein activity is reduced and ultimately the editing process in <i>L. donovani</i> is disturbed and it will inhibit the growth. RNA editing factors are RNA-linked proteins essential for <i>in vivo</i> editing i.e. mitochondrial RNA binding protein1 (MRP 1) originally called as gBP21. The model of <i>L. donovani</i> gBP21 (gBP21Ldv) showed that this protein bears an anti-parallel ß sheet (segregated α and ß regions) with ß-ß-ß-ß-α-ß-ß-ß-ß-α-type topology (“whirly” transcription-factor fold). Each of the four ß strands within a given ß-ß-ß-ß-α repeats and form a curved anti-parallel ß-sheet that packs perpendicularly against the sheet from the other repeat. Among all of the computationally screened compounds by the GLIDE program (Schrödinger) and GOLD program hyperoside1a, posaconazole, quercetin, and pentanediol, 427 exhibited higher binding affinities with the modeled gBP21 protein of <i>L. donovani</i>. Ligandfit program <i>(</i>DSv2.5) revealed that DNA, RNA polymerase inhibitors acyclovir, mitomycin C, and daunorubicin have better binding affinity towards gBP21Ldv. These compounds may be given in combination with miltefosine (first line therapy) against patients with VL and other associated disorders like anemia.
DOI: 10.6084/m9.figshare.825490
title: SiRNA sequence model: redesign algorithm based on available genome-wide libraries

description: The evolution of RNA interference (RNAi) and the development of technologies exploiting its biology have enabled scientists to rapidly examine the consequences of depleting a particular gene product in cells. Design tools have been developed based on experimental data to increase the knockdown efficiency of siRNAs. Not all siRNAs that are developed to a given target mRNA are equally effective. Currently available design algorithms take an accession, identify conserved regions among their transcript space, find accessible regions within the mRNA, design all possible siRNAs for these regions, filter them based on multi-scores thresholds, and then perform off-target filtration. These different criteria are used by commercial suppliers to produce siRNA genome-wide libraries for different organisms. In this article, we analyze existing siRNA design algorithms and evaluate weight of design parameters for libraries produced in the last decade. We proved that not all essential parameters are currently applied by siRNA vendors. Based on our evaluation results, we were able to suggest an siRNA sequence pattern. The findings in our study can be useful for commercial vendors improving the design of RNAi constructs, by addressing both the issue of potency and the issue of specificity.
DOI: 10.6084/m9.figshare.825491
title: Insights on pH-dependent conformational changes of mosquito odorant binding proteins by molecular dynamics simulations

description: Chemical recognition plays an important role for the survival and reproduction of many insect species. Odorant binding proteins (OBPs) are the primary components of the insect olfactory mechanism and have been documented to play an important role in the host-seeking mechanism of mosquitoes. They are “transport proteins” believed to transport odorant molecules from the external environment to their respective membrane targets, the olfactory receptors. The mechanism by which this transport occurs in mosquitoes remains a conundrum in this field. Nevertheless, OBPs have proved to be amenable to conformational changes mediated by a pH change in other insect species. In this paper, the effect of pH on the conformational flexibility of mosquito OBPs is assessed computationally using molecular dynamics simulations of a mosquito OBP “CquiOBP1” bound to its pheromone 3OG (PDB ID: 3OGN). Conformational twist of a loop, driven by a set of well-characterized changes in intramolecular interactions of the loop, is demonstrated. The concomitant (i) closure of what is believed to be the entrance of the binding pocket, (ii) expansion of what could be an exit site, and (iii) migration of the ligand towards this putative exit site provide preliminary insights into the mechanism of ligand binding and release of these proteins in mosquitoes. The correlation of our results with previous experimental observations based on NMR studies help us provide a cardinal illustration on one of the probable dynamics and mechanism by which certain mosquito OBPs could deliver their ligand to their membrane-bound receptors at specific pH conditions.
DOI: 10.6084/m9.figshare.825493.v1
title: Membrane undulation induced by NS4A of Dengue virus: a molecular dynamics simulation study

description: Nonstructural protein 4A (NS4A) of Dengue virus (DENV) is a membrane protein involved in rearrangements of the endoplasmic reticulum membrane that are required for formation of replication vesicles. NS4A is composed most likely of three membrane domains. The N- and C-terminal domains are supposed to traverse the lipid membrane whereas the central one is thought to reside on the membrane surface, thus forming a <i>u</i>-shaped protein. All three membrane domains are proposed to be helical by secondary structure prediction programs. After performing multi nanosecond molecular dynamics (MD) simulations at various temperatures (300, 310, and 315.15 K) with each of the individual domains, they are used in a docking approach to define putative association motifs of the transmembrane domains (TMDs). Two structures of the <i>u</i>-shaped protein are generated by separating two assembled TMDs linking them with the membrane-attached domain. Lipid undulation is monitored with the structures embedded in a fully hydrated lipid bilayer applying multiple 200 ns MD simulations at 310 K. An intact structure of the protein supports membrane undulation. The strong unwinding of the helices in the domain-linking section of one of the structures lowers its capability to induce membrane curvature. Unwinding of the link region is due to interactions of two tryptophan residues, Trp-96 and 104. These results provide first insights into the membrane-altering properties of DENV NS4A.
DOI: 10.6084/m9.figshare.825490.v2
title: SiRNA sequence model: redesign algorithm based on available genome-wide libraries

description: The evolution of RNA interference (RNAi) and the development of technologies exploiting its biology have enabled scientists to rapidly examine the consequences of depleting a particular gene product in cells. Design tools have been developed based on experimental data to increase the knockdown efficiency of siRNAs. Not all siRNAs that are developed to a given target mRNA are equally effective. Currently available design algorithms take an accession, identify conserved regions among their transcript space, find accessible regions within the mRNA, design all possible siRNAs for these regions, filter them based on multi-scores thresholds, and then perform off-target filtration. These different criteria are used by commercial suppliers to produce siRNA genome-wide libraries for different organisms. In this article, we analyze existing siRNA design algorithms and evaluate weight of design parameters for libraries produced in the last decade. We proved that not all essential parameters are currently applied by siRNA vendors. Based on our evaluation results, we were able to suggest an siRNA sequence pattern. The findings in our study can be useful for commercial vendors improving the design of RNAi constructs, by addressing both the issue of potency and the issue of specificity.
DOI: 10.6084/m9.figshare.825490.v1
title: SiRNA sequence model: redesign algorithm based on available genome-wide libraries

description: The evolution of RNA interference (RNAi) and the development of technologies exploiting its biology have enabled scientists to rapidly examine the consequences of depleting a particular gene product in cells. Design tools have been developed based on experimental data to increase the knockdown efficiency of siRNAs. Not all siRNAs that are developed to a given target mRNA are equally effective. Currently available design algorithms take an accession, identify conserved regions among their transcript space, find accessible regions within the mRNA, design all possible siRNAs for these regions, filter them based on multi-scores thresholds, and then perform off-target filtration. These different criteria are used by commercial suppliers to produce siRNA genome-wide libraries for different organisms. In this article, we analyze existing siRNA design algorithms and evaluate weight of design parameters for libraries produced in the last decade. We proved that not all essential parameters are currently applied by siRNA vendors. Based on our evaluation results, we were able to suggest an siRNA sequence pattern. The findings in our study can be useful for commercial vendors improving the design of RNAi constructs, by addressing both the issue of potency and the issue of specificity.
DOI: 10.6084/m9.figshare.825491.v2
title: Insights on pH-dependent conformational changes of mosquito odorant binding proteins by molecular dynamics simulations

description: Chemical recognition plays an important role for the survival and reproduction of many insect species. Odorant binding proteins (OBPs) are the primary components of the insect olfactory mechanism and have been documented to play an important role in the host-seeking mechanism of mosquitoes. They are “transport proteins” believed to transport odorant molecules from the external environment to their respective membrane targets, the olfactory receptors. The mechanism by which this transport occurs in mosquitoes remains a conundrum in this field. Nevertheless, OBPs have proved to be amenable to conformational changes mediated by a pH change in other insect species. In this paper, the effect of pH on the conformational flexibility of mosquito OBPs is assessed computationally using molecular dynamics simulations of a mosquito OBP “CquiOBP1” bound to its pheromone 3OG (PDB ID: 3OGN). Conformational twist of a loop, driven by a set of well-characterized changes in intramolecular interactions of the loop, is demonstrated. The concomitant (i) closure of what is believed to be the entrance of the binding pocket, (ii) expansion of what could be an exit site, and (iii) migration of the ligand towards this putative exit site provide preliminary insights into the mechanism of ligand binding and release of these proteins in mosquitoes. The correlation of our results with previous experimental observations based on NMR studies help us provide a cardinal illustration on one of the probable dynamics and mechanism by which certain mosquito OBPs could deliver their ligand to their membrane-bound receptors at specific pH conditions.