Evaluating the Efficiency of the Martini Force Field to Study Protein
Evaluating the Efficiency of the Martini Force Field to Study Protein Dimerization in Aqueous and Membrane Environments
Protein-protein complex assembly is one of the major drivers of biological response. Understanding the mechanisms of protein oligomerization/dimerization would allow one to elucidate how these complexes participate in biological activities and could ultimately lead to new approaches in designing novel therapeutic agents.
However, determining the exact association pathways and structures of such complexes remains a challenge. Here, we use parallel tempering metadynamics simulations in the well-tempered ensemble to evaluate the performance of Martini 2.2P and Martini open-beta 3 (Martini 3) force fields in reproducing the structure and energetics of the dimerization process of membrane proteins and proteins in an aqueous solution in reasonable accuracy and throughput.
We find that Martini 2.2P systematically overestimates the free energy of association by estimating large barriers in distinct areas, which likely leads to overaggregation when multiple monomers are present. In comparison, the less viscous Martini 3 results in a systematic underestimation of the free energy of association for proteins in solution, while it performs well in describing the association of membrane proteins. In all cases, the near-native dimer complexes are identified as minima in the free energy surface albeit not always as the lowest minima.
In the case of Martini 3, we find that the spurious supramolecular protein aggregation present in Martini 2.2P multimer simulations is alleviated and thus this force field may be more suitable for the study of protein oligomerization. We propose that the use of enhanced sampling simulations with a refined coarse-grained force field and appropriately defined collective variables is a robust approach for studying the protein dimerization process, although one should be cautious of the ranking of energy minima.
Nuclear Pore Complex Proteins/Nup107 |
|||
| E8ER1914-18 | EnoGene | 100ul | EUR 275 |
|
Description: Available in various conjugation types. |
|||
Nuclear Pore Complex Proteins/Nup107 |
|||
| MBS8578104-01mL | MyBiosource | 0.1mL | EUR 345 |
Nuclear Pore Complex Proteins/Nup107 |
|||
| MBS8578104-01mLAF405L | MyBiosource | 0.1mL(AF405L) | EUR 565 |
Nuclear Pore Complex Proteins/Nup107 |
|||
| MBS8578104-01mLAF405S | MyBiosource | 0.1mL(AF405S) | EUR 565 |
Nuclear Pore Complex Proteins/Nup107 |
|||
| MBS8578104-01mLAF610 | MyBiosource | 0.1mL(AF610) | EUR 565 |
Nuclear Pore Complex Proteins/Nup107 |
|||
| MBS8578104-01mLAF635 | MyBiosource | 0.1mL(AF635) | EUR 565 |
Nuclear pore complex protein Nup153 Antibody (FITC) |
|||
| abx107146-100g | Abbexa | 100 µg | EUR 362.5 |
Nuclear pore complex protein Nup153 Antibody (FITC) |
|||
| 20-abx107146 | Abbexa |
|
|
Nuclear pore complex protein Nup153 Antibody (FITC) |
|||
| abx107146-20g | Abbexa | 20 µg | EUR 162.5 |
Nuclear pore complex protein Nup153 Antibody (FITC) |
|||
| abx107146-50g | Abbexa | 50 µg | EUR 250 |
Promoter switching in response to changing environment and elevated expression of protein-coding genes overlapping at their 5′ ends
Despite the number of studies focused on sense-antisense transcription, the key question of whether such organization evolved as a regulator of gene expression or if this is only a byproduct of other regulatory processes has not been elucidated to date. In this study, protein-coding sense-antisense gene pairs were analyzed with a particular focus on pairs overlapping at their 5′ ends. Analyses were performed in 73 human transcription start site libraries. The results of our studies showed that the overlap between genes is not a stable feature and depends on which TSSs are utilized in a given cell type.
An analysis of gene expression did not confirm that overlap between genes causes downregulation of their expression. This observation contradicts earlier findings. In addition, we showed that the switch from one promoter to another, leading to genes overlap, may occur in response to changing environment of a cell or tissue. We also demonstrated that in transfected and cancerous cells genes overlap is observed more often in comparison with normal tissues. Moreover, utilization of overlapping promoters depends on particular state of a cell and, at least in some groups of genes, is not merely coincidental.
The Effect of Rosuvastatin on plasma/serum levels of high sensitivity C-reactive protein, Interleukin-6 and D-dimer in people living with Human Immunodeficiency Virus: a systematic review and meta-analysis
Introduction: Rosuvastatin therapy might have effect on inflammatory and coagulation biomarkers. However, the evidence about the effect of Rosuvastatin therapy on the high sensitivity C-reactive protein (hsCRP), Interleukin-6 (IL-6) and D-dimer levels among people living with Human Immunodeficiency Virus (PLHIV) is still unclear. Therefore, this study investigated the relational effect of Rosuvastatin therapy on serum/plasma hsCRP, IL-6 and D-dimer levels in PLHIV.
Methods: The literature search was done from Embase, PUBMED, and Web of Science databases. The review and meta-analysis included studies written in English language up to 4th January 2020. Random effect model was used to evaluate the pooled standard mean difference with 95% confidence interval.
Results: A meta-analysis was performed using nine articles with 392 PLHIV. The result revealed that the plasma/serum levels of IL-6 were significantly reduced after the intervention. However, hsCRP and D-dimer levels showed no significant difference (p>0.05) between before and after the intervention. The subgroup analysis showed that there was significant association between PLHIV ages <45 years and cohort studies with IL-6 levels.
The current CD4+ counts ≥350 cells/mm3 correlated with hsCRP as well as IL-6. Similarly, nadir CD4+ counts ≥200 cells/mm3 and duration of HIV diagnosis <10 years also showed significant association with IL-6 and D-dimer levels. It was also indicated that participants who were under ART for <7 years were significantly associated with hsCRP levels.
Conclusion: This study established that IL-6 levels were significantly reduced after the intervention whilst hsCRP and D-dimer levels showed no significant difference between before and after the intervention.
Pharmacological inhibition of dynamin-related protein 1 attenuates skeletal muscle insulin resistance in obesity
Dynamin-related protein-1 (Drp1) is a key regulator in mitochondrial fission. Excessive Drp1-mediated mitochondrial fission in skeletal muscle under the obese condition is associated with impaired insulin action. However, it remains unknown whether pharmacological inhibition of Drp1, using the Drp1-specific inhibitor Mitochondrial Division Inhibitor 1 (Mdivi-1), is effective in alleviating skeletal muscle insulin resistance and improving whole-body metabolic health under the obese and insulin-resistant condition. We subjected C57BL/6J mice to a high-fat diet (HFD) or low-fat diet (LFD) for 5-weeks. HFD-fed mice received Mdivi-1 or saline injections for the last week of the diet intervention.
Additionally, myotubes derived from obese insulin-resistant humans were treated with Mdivi-1 or saline for 12 h. We measured glucose area under the curve (AUC) from a glucose tolerance test (GTT), skeletal muscle insulin action, mitochondrial dynamics, respiration, and H2 O2 content. We found that Mdivi-1 attenuated impairments in skeletal muscle insulin signaling and blood glucose AUC from a GTT induced by HFD feeding (p < 0.05). H2 O2 content was elevated in skeletal muscle from the HFD group (vs. LFD, p < 0.05), but was reduced with Mdivi-1 treatment, which may partially explain the improvement in skeletal muscle insulin action.
Similarly, Mdivi-1 enhanced the mitochondrial network structure, reduced reactive oxygen species, and improved insulin action in myotubes from obese humans (vs. saline, p < 0.05). In conclusion, inhibiting Drp1 with short-term Mdivi-1 administration attenuates the impairment in skeletal muscle insulin signaling and improves whole-body glucose tolerance in the setting of obesity-induced insulin resistance. Targeting Drp1 may be a viable approach to treat obesity-induced insulin resistance.