Dataset Information

Molecular docking based screening of Noggin inhibitors.

ABSTRACT: Noggin (NOG) a BMP (bone morphogenetic protein) antagonist plays a key role in preferentially driving a subset of breast cancer cells towards the bone and causing osteolytic lesions leading to severe pain and discomfort in the patients. Owing to its role in bone metastasis, NOG could be promising molecular target in bone metastasis and that identifying small molecule inhibitors could aid in the treatment. Towards identifying cognate inhibitors of NOG, structure based virtual screen was employed. A total of 8.5 million ligands from e-molecule database were screened at a novel binding site on NOG identified by the Sitemap tool, employing GLIDE algorithm. Potential eight molecules were selected based on the Glide score, binding mode and H-bond interactions. Free energy of binding was calculated using Molecular mechanics based MMGBSA and the obtained energy was used in the prioritizing the compounds with the similar structures and glide score. Further, the compounds were evaluated for their druggability employing physico-chemical property analysis. Our study helped in identifying novel potential NOG inhibitors that can further be validated using in-vivo and in-vitro studies and these molecules can also be employed as tool compounds to study the functions of BMP.

SUBMITTER: Gudipati S

PROVIDER: S-EPMC5818642 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Molecular docking based screening of Noggin inhibitors.

Gudipati Sindhura S Muttineni Ravi R Mankad Archana Uday AU Pandya Himanshu Aniruddha HA Jasrai Yogesh Trilokinath YT

Bioinformation 20180131 1

Noggin (NOG) a BMP (bone morphogenetic protein) antagonist plays a key role in preferentially driving a subset of breast cancer cells towards the bone and causing osteolytic lesions leading to severe pain and discomfort in the patients. Owing to its role in bone metastasis, NOG could be promising molecular target in bone metastasis and that identifying small molecule inhibitors could aid in the treatment. Towards identifying cognate inhibitors of NOG, structure based virtual screen was employed. ...[more]

PMID: 29497255

Similar Datasets

Project description:UnlabelledThe present antipsychotic drugs have known to show serious concerns like extra pyramidal side effects therefore, pursuit for novel antipsychotic GABAnergic drugs has lately focused on the folkloric medicine from plant derivatives as better treatment option of schizophrenia. The present study centers to identify potential inhibitors of plant origin for GABA receptor through in silico approaches. Three compound datasets were undertaken in the study. The first set consisted of seven compounds which included Magnolol, Honokiol and other plant derivatives. The second set consisted of 16 derivatives of N-diarylalkenyl-piperidinecarboxylic acid synthesized by Zheng et al., 2006. The third dataset had thirty two compounds which were Magnolol and Honokiol analogues synthesized by Fuchs et al., 2014. All the compounds were docked at the allosteric site of the GABA (A) receptor. The compounds were further tested for ADMET and biological activity. We observed Honokiol and its derivatives demonstrated superior druglike properties than any compound undertaken in the study. Further, compound 61 [2-(4-methoxyphenyl)-4-propylphenol] of dataset three - a synthetic derivative of honokiol had better profile than its parent compound. In a possible attempt to identify compound with even better efficacious compound than 61, virtual screening was performed, 135 compounds akin to compound 61 were retrieved. Interestingly none of the 135 compounds showed better druggable properties than compound 61. Our in silico pharmacological profiling of compounds is in coherence and is complemented by the findings of Fuchs et al, which also revealed compound 61 to be the good potentiator of GABA receptor.AbbreviationsGABA (A) R - Gamma Amino Butyric Acid Receptor, subtype A, GPCR - G Protein Coupled Receptor, OPLS - Optimized Potentials for Liquid Simulations, PDB - Protein Data Bank, PLP - Piece wise Linear Potential, T.E.S.T - Toxicity Estimation Software Tool, TCM - Traditional Chinese Medicine.

Dataset Information

Molecular docking based screening of Noggin inhibitors.

Publications

Molecular docking based screening of Noggin inhibitors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets