| Title |
Homology modelling, molecular docking, and molecular dynamics simulations reveal the inhibition of Leishmania donovani dihydrofolate reductase-thymidylate synthase enzyme by Withaferin-A
|
|---|---|
| Published in |
BMC Research Notes, April 2018
|
| DOI | 10.1186/s13104-018-3354-1 |
| Pubmed ID | |
| Authors |
Bharadwaja Vadloori, A. K. Sharath, N. Prakash Prabhu, Radheshyam Maurya |
| Abstract |
Present in silico study was carried out to explore the mode of inhibition of Leishmania donovani dihydrofolate reductase-thymidylate synthase (Ld DHFR-TS) enzyme by Withaferin-A, a withanolide isolated from Withania somnifera. Withaferin-A (WA) is known for its profound multifaceted properties, but its antileishmanial activity is not well understood. The parasite's DHFR-TS enzyme is diverse from its mammalian host and could be a potential drug target in parasites. A 3D model of Ld DHFR-TS enzyme was built and verified using Ramachandran plot and SAVES tools. The protein was docked with WA-the ligand, methotrexate (MTX)-competitive inhibitor of DHFR, and dihydrofolic acid (DHFA)-substrate for DHFR-TS. Molecular docking studies reveal that WA competes for active sites of both Hu DHFR and TS enzymes whereas it binds to a site other than active site in Ld DHFR-TS. Moreover, Lys 173 residue of DHFR-TS forms a H-bond with WA and has higher binding affinity to Ld DHFR-TS than Hu DHFR and Hu TS. The MD simulations confirmed the H-bonding interactions were stable. The binding energies of WA with Ld DHFR-TS were calculated using MM-PBSA. Homology modelling, molecular docking and MD simulations of Ld DHFR-TS revealed that WA could be a potential anti-leishmanial drug. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 70 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 70 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 11 | 16% |
| Researcher | 11 | 16% |
| Student > Bachelor | 10 | 14% |
| Student > Master | 5 | 7% |
| Professor > Associate Professor | 3 | 4% |
| Other | 9 | 13% |
| Unknown | 21 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 20 | 29% |
| Chemistry | 7 | 10% |
| Agricultural and Biological Sciences | 5 | 7% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 4% |
| Engineering | 3 | 4% |
| Other | 6 | 9% |
| Unknown | 26 | 37% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 April 2018.
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#20,481,952
of 23,043,346 outputs
Outputs from BMC Research Notes
#3,581
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#262,194
of 296,868 outputs
Outputs of similar age from BMC Research Notes
#83
of 99 outputs
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