The Binding Mode Prediction and Similar Ligand Potency in the Active Site of Vitamin D Receptor with <scp>QM</scp>/<scp>MM</scp> Interaction, <scp>MESP</scp>, and <scp>MD</scp> Simulation

Nagamani, Selvaraman; Selvam, S.; Muthusamy, Karthikeyan

doi:10.1111/cbdd.12754

Cited by 10 publications

(2 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…So, in the presence of metformin, the reactivity of vitamin D in the binding site of VDR is increased. Based on a prior QM/MM study conducted on some VDR agonists, compounds with lower HOMO and LUMO had the higher affinities to bond to VDR [42]. Upon data shown in Table 3, in the presence of metformin, the HOMO of vitamin D was lower than the HOMO of vitamin D in the absence of metformin.…”

Section: Qm/mm Computations On Vitamin D In Free and Vdr Bound Statesmentioning

confidence: 94%

Vitamin D as a modulating agent of metformin and insulin in patients with type 2 diabetes

Abdi¹,

Movahedi²,

Nikje³

et al. 2019

jrp

View full text Add to dashboard Cite

Diabetes, which is one of the most important health challenges for humankind, is associated with impaired glucose metabolism. Diabetes mellitus (DM) includes two major types of diabetes, type 1 (T1DM) and type 2 (T2DM). In this study, in the beginning, interventional and experimental studies were performed on 45 patients with T2DM, and the modulating effects of vitamin D were evaluated on the biochemical parameters of patients with the restricted diet, consuming metformin or insulin. With regard to our experimental results, the combination treatment of metformin/ vitamin D or insulin/ vitamin D can reduce the fasting blood sugar (FBS). A combination of vitamin D with insulin decreases the insulin resistance and raises the insulin sensitivity in patients with T2DM. The combination treatment of vitamin D and metformin led to a decrease in the level of mRNA of GLUT4, and also it's trafficking from the cytosol to the plasma membrane. At the second phase of the present study, molecular dynamics (MD), molecular docking, MM/PBSA, and QM/MM were occupied to examine the structural behavior of VDR, in the free or ligand bound state, during 50 ns. The MD results exhibited that in the presence of metformin, the flexibility of residues comprising helix 12 from vitamin D-bound VDR was decreased. In addition, metformin decreased the radius of gyration of agonist-bound VDR. In addition, QM/MM results showed that metformin diminished the binding free energy between VDR and vitamin D. Our computational data demonstrated that metformin, in the presence of vitamin D, reinforces the interaction between VDR and its co-activator protein.

show abstract

Section: Qm/mm Computations On Vitamin D In Free and Vdr Bound Statesmentioning

confidence: 94%

Vitamin D as a modulating agent of metformin and insulin in patients with type 2 diabetes

Abdi¹,

Movahedi²,

Nikje³

et al. 2019

jrp

View full text Add to dashboard Cite

show abstract

“…The strength of transcription can also be influenced by structural changes to the VDRM backbone [ 8 , 9 ]. Non-secosteroidal ligands are known to be VDR agonists [ 10 ]. VDR antagonists and partial agonists are typically based on the secosteroid scaffold of calcitriol, and only a few non-secosteroidal VDR antagonists are known [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Calcitriol and Vitamin D Receptor Modulator 2 on Recovery of Injured Skeletal Muscle in Wistar Rats

Stratos,

Schleese,

Rinas

et al. 2023

Biomedicines

View full text Add to dashboard Cite

Muscle injuries often result in functional limitations due to insufficient healing. This study assessed the influence of calcitriol and vitamin D Receptor Modulator 2 (VDRM2) on muscle regeneration in male Wistar rats following open blunt muscle injury. The injured left soleus muscle of the rats was treated for the first four days after trauma with local injections of either calcitriol, VDRM2, or a 10% ethanol solution (control). Although muscle strength significantly decreased post-injury, all groups showed gradual improvement but did not achieve full recovery. By the 14th day, calcitriol-treated rats significantly outperformed the control group in the incomplete tetanic force, with VDRM2-treated rats showing muscle strength values that fell between the control and calcitriol groups. Similar trends were observed in complete tetanic contractions and were confirmed histologically via muscle cell width quantification. Additionally, histological analysis showed increased cellular turnover on the fourth postoperative day in the calcitriol group, as indicated by elevated cell proliferation rates and fewer apoptotic cells. VDRM2-treated animals showed only an increased proliferative activity on day 4 after injury. No noticeable differences between the groups for CAE-positive cells or visible muscle tissue area were found. In conclusion, predominantly calcitriol positively influenced post-trauma muscle recovery, where VDRM2 had substantially lower biological activity.

show abstract

Structural and functional insights on vitamin D receptor and CYP24A1 deleterious single nucleotide polymorphisms: A computational and pharmacogenomics perpetual approach

Jayaraj

Kuriakose

Alhazmi

et al. 2021

Cell Biochemistry & Function

Self Cite

View full text Add to dashboard Cite

The development of chronic kidney disease (CKD) drugs remains a challenge due to the variations in the genes. The vitamin D receptor (VDR) and Cytochrome 24A1 (CYP24A1) genetic variants might affect the drug potency, efficacy and pathway.Here we have to analyse and determine the deleterious single-nucleotide polymorphisms (nsSNPs) of VDR and CYP24A1 genes and their different population's drug responses in different populations to understand the key role in CKD. Among that the large scale of nsSNP, we used certain computational tools that predicted six missense variants are observed to be significantly damaging effect and SNP variability with large differences in various populations. Molecular docking studies were carried out by clinical and our screened compounds to VDR and CYP24A1. Docking results revealed all the compounds have a good binding affinity (Score). The screened compounds (TCM_2868 and UNPD_141613) show good binding affinity when compared to known compounds. The QM/MM study revealed that the compounds have electron transfer ability and act as a donor/acceptor to mutated proteins. The structural and conformational changes of protein complexes were analysed by molecular dynamics study. Hence, this study helps to identify suitable drugs through drug discovery in CKD treatment. The abovementioned compounds have more binding affinity, efficacy, and potency of both wild and mutant of VDR and CYP24A1.

show abstract

The Binding Mode Prediction and Similar Ligand Potency in the Active Site of Vitamin D Receptor with QM/MM Interaction, MESP, and MD Simulation

Cited by 10 publications

References 54 publications

Vitamin D as a modulating agent of metformin and insulin in patients with type 2 diabetes

Vitamin D as a modulating agent of metformin and insulin in patients with type 2 diabetes

Effect of Calcitriol and Vitamin D Receptor Modulator 2 on Recovery of Injured Skeletal Muscle in Wistar Rats

Structural and functional insights on vitamin D receptor and CYP24A1 deleterious single nucleotide polymorphisms: A computational and pharmacogenomics perpetual approach

Contact Info

Product

Resources

About