Histone deacetylase 3 (HDAC3) has been recently identified as a potential target for the treatment of cancer and other diseases, such as chronic inflammation, neurodegenerative diseases, and diabetes. Virtual screening (VS) is currently a routine technique for hit identification, but its success depends on rational development of VS strategies. To facilitate this process, we applied our previously released benchmarking dataset, i.e., MUBD-HDAC3 to the evaluation of structure-based VS (SBVS) and ligand-based VS (LBVS) combinatorial approaches. We have identified FRED (Chemgauss4) docking against a structural model of HDAC3, i.e., SAHA-3 generated by a computationally inexpensive “flexible docking”, as the best SBVS approach and a common feature pharmacophore model, i.e., Hypo1 generated by Catalyst/HipHop as the optimal model for LBVS. We then developed a pipeline that was composed of Hypo1, FRED (Chemgauss4), and SAHA-3 sequentially, and demonstrated that it was superior to other combinations in terms of ligand enrichment. In summary, we present the first highly-validated, rationally-designed VS strategy specific to HDAC3 inhibitor discovery. The constructed pipeline is publicly accessible for the scientific community to identify novel HDAC3 inhibitors in a time-efficient and cost-effective way.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2jYXXe6
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
The trehalose biosynthetic pathway is of great interest for the development of novel therapeutics because trehalose is an essential disaccha...
-
British Journal of Oral and Maxillofacial Surgery... Stem Cells and DevelopmentMesenchymal Stem/Stroma... [ASAP] Self-Assembly of Giant Mo...
-
Chandigarh Tribune Watch that mouth, literally Chandigarh Tribune When talking about cancer , we usually think of cancer of the blo...
-
BRAF mutation testing to determine eligibility for treatment with vemurafenib was performed on archival skin lesions of a 54-year-old patien...
-
Abstract ᅟ http://ift.tt/2pGNeby
-
The efficacy and optimization of poststroke physical therapy paradigms is challenged in part by a lack of objective tools available to resea...
-
Robert Schumann regnes som en av de store romantiske komponistene, særlig anerkjent er hans klaver- og kammermusikk. Han startet på utdanni...
-
Abstract Laser-induced acoustic desorption (LIAD) allows for desorption of neutral nonvolatile compounds independent of their volatility o...
-
Abstract Background Transanal minimally invasive surgery (TAMIS) has gained worldwide popularity as a method for the local excision of r...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου