cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.825937.v2
title: Patterns of floristic composition of Mediterranean meadows and mesophytic grasslands in eastern Continental Portugal

description: It is becoming increasingly necessary to gain a deeper understanding of the ecological gradients underlying the floristic pattern of meadows and grasslands, because their distribution area and dynamics may be affected by the increased dryness resulting from climate change. Thus, the objectives are (1) to identify community types in <i>Molinio–Arrhenatheretea</i> meadows and <i>Stipo giganteae–Agrostietea castellanae</i> grasslands in Eastern Continental Portugal; (2) to recognize those communities that configure habitat types of the European Union Habitats Directive; (3) to establish environmental gradients underlying their spatial variation. Combining the Braun–Blanquet approach with numerical analysis, 292 relevés and 448 species were classified and ordered using two-way indicator species analysis (Twinspan classification) and canonical correspondence analysis (CCA). Partial CCA was applied to assess the relative influence of land use factors. About 17 community types were identified and those floristic patterns were mainly related to environmental gradients linked to pedological factors and humidity gradients. Based on biogeography and the determination of diagnostic species, four new phytosociological associations were proposed: <i>Mentho pulegii–Cyperetum badii</i> ass. nova hoc loco; <i>Trifolio resupinati–Menthetum suaveolentis</i> ass. nova hoc loco; <i>Mentho suaveolentis–Holcetum lanati</i> ass. nova hoc loco and <i>Festuco amplae–Brachypodietum phoenicoidis</i> ass. nova hoc loco.
DOI: 10.6084/m9.figshare.825934.v1
title: Role of ELA region in auto-activation of mutant KIT receptor: a molecular dynamics simulation insight

description: KIT receptor is the prime target in gastrointestinal stromal tumor (GISTs) therapy. Second generation inhibitor, Sunitinib, binds to an inactivated conformation of KIT receptor and stabilizes it in order to prevent tumor formation. Here, we investigated the dynamic behavior of wild type and mutant D816H KIT receptor, and emphasized the extended A-loop (EAL) region (805–850) by conducting molecular dynamics simulation (∼100 ns). We analyzed different properties such as root mean square cutoff or deviation, root mean square fluctuation, radius of gyration, solvent-accessible surface area, hydrogen bonding network analysis, and essential dynamics. Apart from this, clustering and cross-correlation matrix approach was used to explore the conformational space of the wild type and mutant EAL region of KIT receptor. Molecular dynamics analysis indicated that mutation (D816H) was able to alter intramolecular hydrogen bonding pattern and affected the structural flexibility of EAL region. Moreover, flexible secondary elements, specially, coil and turns were dominated in EAL region of mutant KIT receptor during simulation. This phenomenon increased the movement of EAL region which in turn helped in shifting the equilibrium towards the active kinase conformation. Our atomic investigation of mutant KIT receptor which emphasized on EAL region provided a better insight into the understanding of Sunitinib resistance mechanism of KIT receptor and would help to discover new therapeutics for KIT-based resistant tumor cells in GIST therapy.
DOI: 10.6084/m9.figshare.825922
title: Comparative molecular dynamics simulation studies for determining factors contributing to the thermostability of chemotaxis protein “CheY”

description: Comparative molecular dynamics simulations of chemotaxis protein “CheY” from thermophilic origin <i>Thermotoga maritima</i> and its mesophilic counterpart <i>Salmonella enterica</i> have been performed for 10 ns each at 300 and 350 K, and 20 ns each at 400 and 450 K. The trajectories were analyzed in terms of different factors like root-mean-square deviation, root-mean-square fluctuation, radius of gyration, solvent accessible surface area, H-bonds, salt bridge content, and protein–solvent interactions which indicate distinct differences between the two of them. The two proteins also follow dissimilar unfolding pathways. The overall flexibility calculated by the trace of the diagonalized covariance matrix displays similar flexibility of both the proteins near their optimum growth temperatures. However, at higher temperatures mesophilic protein shows increased overall flexibility than its thermophilic counterpart. Principal component analysis also indicates that the essential subspaces explored by the simulations of two proteins at different temperatures are nonoverlapping and they show significantly different directions of motion. However, there are significant overlaps within the trajectories and similar direction of motions are observed for both proteins at 300 K. Overall, the mesophilic protein leads to increased conformational sampling of the phase space than its thermophilic counterpart. This is the first ever study of thermostability of CheY protein homologs by using protein dynamism as a main impact. Our study might be used as a model for studying the molecular basis of thermostability of two homologous proteins from two organisms living at different temperatures with less visible differences.
DOI: 10.6084/m9.figshare.825922.v2
title: Comparative molecular dynamics simulation studies for determining factors contributing to the thermostability of chemotaxis protein “CheY”

description: Comparative molecular dynamics simulations of chemotaxis protein “CheY” from thermophilic origin <i>Thermotoga maritima</i> and its mesophilic counterpart <i>Salmonella enterica</i> have been performed for 10 ns each at 300 and 350 K, and 20 ns each at 400 and 450 K. The trajectories were analyzed in terms of different factors like root-mean-square deviation, root-mean-square fluctuation, radius of gyration, solvent accessible surface area, H-bonds, salt bridge content, and protein–solvent interactions which indicate distinct differences between the two of them. The two proteins also follow dissimilar unfolding pathways. The overall flexibility calculated by the trace of the diagonalized covariance matrix displays similar flexibility of both the proteins near their optimum growth temperatures. However, at higher temperatures mesophilic protein shows increased overall flexibility than its thermophilic counterpart. Principal component analysis also indicates that the essential subspaces explored by the simulations of two proteins at different temperatures are nonoverlapping and they show significantly different directions of motion. However, there are significant overlaps within the trajectories and similar direction of motions are observed for both proteins at 300 K. Overall, the mesophilic protein leads to increased conformational sampling of the phase space than its thermophilic counterpart. This is the first ever study of thermostability of CheY protein homologs by using protein dynamism as a main impact. Our study might be used as a model for studying the molecular basis of thermostability of two homologous proteins from two organisms living at different temperatures with less visible differences.
DOI: 10.6084/m9.figshare.825922.v1
title: Comparative molecular dynamics simulation studies for determining factors contributing to the thermostability of chemotaxis protein “CheY”

description: Comparative molecular dynamics simulations of chemotaxis protein “CheY” from thermophilic origin <i>Thermotoga maritima</i> and its mesophilic counterpart <i>Salmonella enterica</i> have been performed for 10 ns each at 300 and 350 K, and 20 ns each at 400 and 450 K. The trajectories were analyzed in terms of different factors like root-mean-square deviation, root-mean-square fluctuation, radius of gyration, solvent accessible surface area, H-bonds, salt bridge content, and protein–solvent interactions which indicate distinct differences between the two of them. The two proteins also follow dissimilar unfolding pathways. The overall flexibility calculated by the trace of the diagonalized covariance matrix displays similar flexibility of both the proteins near their optimum growth temperatures. However, at higher temperatures mesophilic protein shows increased overall flexibility than its thermophilic counterpart. Principal component analysis also indicates that the essential subspaces explored by the simulations of two proteins at different temperatures are nonoverlapping and they show significantly different directions of motion. However, there are significant overlaps within the trajectories and similar direction of motions are observed for both proteins at 300 K. Overall, the mesophilic protein leads to increased conformational sampling of the phase space than its thermophilic counterpart. This is the first ever study of thermostability of CheY protein homologs by using protein dynamism as a main impact. Our study might be used as a model for studying the molecular basis of thermostability of two homologous proteins from two organisms living at different temperatures with less visible differences.
DOI: 10.6084/m9.figshare.825903
title: Simulation of the cavity-binding site of three bacterial multicopper oxidases upon complex stabilization: interactional profile and electron transference pathways

description: Previous studies have shown that multicopper oxidases (MCOs) oxidize organic and inorganic compounds through oxidation–reduction reactions in which three structurally and functionally arranged copper centers coordinate the uptake of an electron from a reduced substrate. Structural comparisons among three bacterial MCOs, with high structural homology and available three-dimensional information, reveal that the primary structural differences between these MCOs are located near the mononuclear copper center (T1Cu), where substrate oxidation occurs, as opposed to where the reduction of oxygen to water occurs at the trinuclear center. Nevertheless, this substrate oxidation is achieved through an outer-sphere electron transfer mechanism that does not generate a stable substrate–enzyme complex. In this study, MCOs from <i>Thermus thermophilus</i> (<i>Tth</i>-MCO), <i>Bacillus subtilis</i> (CotA), and <i>Escherichia coli</i> (CueO), which have been previously determined through X-ray crystallography, were used as models to analyze the binding modes of these MCOs to three organic molecules, with specific interest in the substrate-binding site. The binding mode of the electron-donor molecule to the electron transfer binding site was primarily attributed to hydrophobic contacts, which likely play an important role in the determination of substrate specificity. Some complexes generated in this study showed an electron donor molecule conformation in which an electron could be directly transferred to the histidines coordinating T1Cu, while for others additional electron transference pathways were also possible through the participation of charged residues during electron transfer.
DOI: 10.6084/m9.figshare.825903.v2
title: Simulation of the cavity-binding site of three bacterial multicopper oxidases upon complex stabilization: interactional profile and electron transference pathways

description: Previous studies have shown that multicopper oxidases (MCOs) oxidize organic and inorganic compounds through oxidation–reduction reactions in which three structurally and functionally arranged copper centers coordinate the uptake of an electron from a reduced substrate. Structural comparisons among three bacterial MCOs, with high structural homology and available three-dimensional information, reveal that the primary structural differences between these MCOs are located near the mononuclear copper center (T1Cu), where substrate oxidation occurs, as opposed to where the reduction of oxygen to water occurs at the trinuclear center. Nevertheless, this substrate oxidation is achieved through an outer-sphere electron transfer mechanism that does not generate a stable substrate–enzyme complex. In this study, MCOs from <i>Thermus thermophilus</i> (<i>Tth</i>-MCO), <i>Bacillus subtilis</i> (CotA), and <i>Escherichia coli</i> (CueO), which have been previously determined through X-ray crystallography, were used as models to analyze the binding modes of these MCOs to three organic molecules, with specific interest in the substrate-binding site. The binding mode of the electron-donor molecule to the electron transfer binding site was primarily attributed to hydrophobic contacts, which likely play an important role in the determination of substrate specificity. Some complexes generated in this study showed an electron donor molecule conformation in which an electron could be directly transferred to the histidines coordinating T1Cu, while for others additional electron transference pathways were also possible through the participation of charged residues during electron transfer.
DOI: 10.6084/m9.figshare.825903.v1
title: Simulation of the cavity-binding site of three bacterial multicopper oxidases upon complex stabilization: interactional profile and electron transference pathways

description: Previous studies have shown that multicopper oxidases (MCOs) oxidize organic and inorganic compounds through oxidation–reduction reactions in which three structurally and functionally arranged copper centers coordinate the uptake of an electron from a reduced substrate. Structural comparisons among three bacterial MCOs, with high structural homology and available three-dimensional information, reveal that the primary structural differences between these MCOs are located near the mononuclear copper center (T1Cu), where substrate oxidation occurs, as opposed to where the reduction of oxygen to water occurs at the trinuclear center. Nevertheless, this substrate oxidation is achieved through an outer-sphere electron transfer mechanism that does not generate a stable substrate–enzyme complex. In this study, MCOs from <i>Thermus thermophilus</i> (<i>Tth</i>-MCO), <i>Bacillus subtilis</i> (CotA), and <i>Escherichia coli</i> (CueO), which have been previously determined through X-ray crystallography, were used as models to analyze the binding modes of these MCOs to three organic molecules, with specific interest in the substrate-binding site. The binding mode of the electron-donor molecule to the electron transfer binding site was primarily attributed to hydrophobic contacts, which likely play an important role in the determination of substrate specificity. Some complexes generated in this study showed an electron donor molecule conformation in which an electron could be directly transferred to the histidines coordinating T1Cu, while for others additional electron transference pathways were also possible through the participation of charged residues during electron transfer.
DOI: 10.6084/m9.figshare.825897
title: Structural and energetic properties of the potential HIV-1 reverse transcriptase inhibitors d4A and d4G: a comprehensive theoretical investigation

description: A comprehensive quantum-chemical investigation of the conformational landscapes of two nucleoside HIV-1 reverse transcriptase inhibitors, 2′,3′-didehydro-2′,3′-dideoxyadenosine (d4A), and 2′,3′-didehydro-2′,3′-dideoxyguanosine (d4G), has been performed at the MP2/6-311++G(d,p)//B3LYP/6-31G(d,p) level of theory. It was found that d4A can adopt 21 conformers within a 5.17 kcal/mol Gibbs free energy range, whereas d4G has 20 conformers within 6.23 kcal/mol at <i>T</i> = 298.15 K. Both nucleosides are shaped by a sophisticated network of specific noncovalent interactions, including conventional (OHO, NHO) and weak (CHO, CHN) hydrogen bonds, as well as dihydrogen (CHHC) contacts. For the OHO, NHO, and CHO hydrogen bonds, natural bond orbital analysis revealed hyperconjugative interactions between the oxygen lone pairs and the antibonding orbital of the donor group. For the CHHC contacts, the electron density migrates from the antibonding orbital, corresponding to the CH group of the sugar residue, to the bonding orbital relative to the same group in the nucleobase. The results confirm the current belief that the biological activity of d4A and d4G is connected with the termination of the DNA chain synthesis in the 5′–3′ direction. Thus, these nucleosides act as competitive HIV-1 reverse transcriptase inhibitors.
DOI: 10.6084/m9.figshare.825897.v2
title: Structural and energetic properties of the potential HIV-1 reverse transcriptase inhibitors d4A and d4G: a comprehensive theoretical investigation

description: A comprehensive quantum-chemical investigation of the conformational landscapes of two nucleoside HIV-1 reverse transcriptase inhibitors, 2′,3′-didehydro-2′,3′-dideoxyadenosine (d4A), and 2′,3′-didehydro-2′,3′-dideoxyguanosine (d4G), has been performed at the MP2/6-311++G(d,p)//B3LYP/6-31G(d,p) level of theory. It was found that d4A can adopt 21 conformers within a 5.17 kcal/mol Gibbs free energy range, whereas d4G has 20 conformers within 6.23 kcal/mol at <i>T</i> = 298.15 K. Both nucleosides are shaped by a sophisticated network of specific noncovalent interactions, including conventional (OHO, NHO) and weak (CHO, CHN) hydrogen bonds, as well as dihydrogen (CHHC) contacts. For the OHO, NHO, and CHO hydrogen bonds, natural bond orbital analysis revealed hyperconjugative interactions between the oxygen lone pairs and the antibonding orbital of the donor group. For the CHHC contacts, the electron density migrates from the antibonding orbital, corresponding to the CH group of the sugar residue, to the bonding orbital relative to the same group in the nucleobase. The results confirm the current belief that the biological activity of d4A and d4G is connected with the termination of the DNA chain synthesis in the 5′–3′ direction. Thus, these nucleosides act as competitive HIV-1 reverse transcriptase inhibitors.
DOI: 10.6084/m9.figshare.825897.v1
title: Structural and energetic properties of the potential HIV-1 reverse transcriptase inhibitors d4A and d4G: a comprehensive theoretical investigation

description: A comprehensive quantum-chemical investigation of the conformational landscapes of two nucleoside HIV-1 reverse transcriptase inhibitors, 2′,3′-didehydro-2′,3′-dideoxyadenosine (d4A), and 2′,3′-didehydro-2′,3′-dideoxyguanosine (d4G), has been performed at the MP2/6-311++G(d,p)//B3LYP/6-31G(d,p) level of theory. It was found that d4A can adopt 21 conformers within a 5.17 kcal/mol Gibbs free energy range, whereas d4G has 20 conformers within 6.23 kcal/mol at <i>T</i> = 298.15 K. Both nucleosides are shaped by a sophisticated network of specific noncovalent interactions, including conventional (OHO, NHO) and weak (CHO, CHN) hydrogen bonds, as well as dihydrogen (CHHC) contacts. For the OHO, NHO, and CHO hydrogen bonds, natural bond orbital analysis revealed hyperconjugative interactions between the oxygen lone pairs and the antibonding orbital of the donor group. For the CHHC contacts, the electron density migrates from the antibonding orbital, corresponding to the CH group of the sugar residue, to the bonding orbital relative to the same group in the nucleobase. The results confirm the current belief that the biological activity of d4A and d4G is connected with the termination of the DNA chain synthesis in the 5′–3′ direction. Thus, these nucleosides act as competitive HIV-1 reverse transcriptase inhibitors.
DOI: 10.6084/m9.figshare.825885
title: <i>Plasmodium falciparum</i> Hsp70-x: a heat shock protein at the host–parasite interface

description: <i>Plasmodium falciparum</i> 70 kDa heat shock proteins (PfHsp70s) are expressed at all stages of the pathogenic erythrocytic phase of the malaria parasite life cycle. There are six PfHsp70s, all of which have orthologues in other plasmodial species, except for PfHsp70-x which is unique to <i>P. falciparum</i>. This research highlights a number of original results obtained by a detailed bioinformatics analysis of the protein. Large-scale sequence analysis indicated the presence of an extended transit peptide sequence of PfHsp70-x which potentially directs it to the endoplasmic reticulum (ER). Further analysis showed that PfHsp70-x does not have an ER-retention sequence, suggesting that the protein transits through the ER and is secreted into the parasitophorous vacuole or beyond into the erythrocyte cytosol. These results are consistent with experimental findings. Next, possible interactions between PfHsp70-x and exported <i>P. falciparum</i> Hsp40s or host erythrocyte Hsp40 were interrogated by modelling and docking. Docking results indicated that interaction between PfHsp70-x and each of the Hsp40s, regardless of biological feasibility, seems equally likely. This suggests that J domain might not provide the specificity in the formation of unique Hsp70-Hsp40 complexes, but that the specificity might be provided by other domains of Hsp40s. By studying different structural conformations of PfHsp70-x, it was shown that Hsp40s can only bind when PfHsp70-x is in a certain conformation. Additionally, this work highlighted the possible dependence of the substrate-binding domain residues on the orientation of the α-helical lid for formation of the substrate-binding pocket.
DOI: 10.6084/m9.figshare.825885.v2
title: <i>Plasmodium falciparum</i> Hsp70-x: a heat shock protein at the host–parasite interface

description: <i>Plasmodium falciparum</i> 70 kDa heat shock proteins (PfHsp70s) are expressed at all stages of the pathogenic erythrocytic phase of the malaria parasite life cycle. There are six PfHsp70s, all of which have orthologues in other plasmodial species, except for PfHsp70-x which is unique to <i>P. falciparum</i>. This research highlights a number of original results obtained by a detailed bioinformatics analysis of the protein. Large-scale sequence analysis indicated the presence of an extended transit peptide sequence of PfHsp70-x which potentially directs it to the endoplasmic reticulum (ER). Further analysis showed that PfHsp70-x does not have an ER-retention sequence, suggesting that the protein transits through the ER and is secreted into the parasitophorous vacuole or beyond into the erythrocyte cytosol. These results are consistent with experimental findings. Next, possible interactions between PfHsp70-x and exported <i>P. falciparum</i> Hsp40s or host erythrocyte Hsp40 were interrogated by modelling and docking. Docking results indicated that interaction between PfHsp70-x and each of the Hsp40s, regardless of biological feasibility, seems equally likely. This suggests that J domain might not provide the specificity in the formation of unique Hsp70-Hsp40 complexes, but that the specificity might be provided by other domains of Hsp40s. By studying different structural conformations of PfHsp70-x, it was shown that Hsp40s can only bind when PfHsp70-x is in a certain conformation. Additionally, this work highlighted the possible dependence of the substrate-binding domain residues on the orientation of the α-helical lid for formation of the substrate-binding pocket.