Premium
Identifying new clotting factor XIa inhibitors in virtual high‐throughput screens using PCA‐GA‐SVM models and signature
Author(s) -
Chen Jonathan J.,
Schmucker Lyndsey N.,
Visco Donald P.
Publication year - 2018
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1002/btpr.2693
Subject(s) - blood clotting , zymogen , clotting factor , virtual screening , pipeline (software) , throughput , computer science , mechanism (biology) , high throughput screening , computational biology , chemistry , biochemistry , biology , drug discovery , medicine , biomedical engineering , enzyme , telecommunications , programming language , philosophy , epistemology , wireless
Blood Clotting Factor XI is an important actor in the clotting mechanism: it activates downstream zymogen involved in the clotting process. It can be targeted for activation or inhibition depending on treatment goals to enhance or inhibit clotting. In terms of antithrombosis treatment, Factor XI has emerged as a promising target to focus on. In this work, an iterative virtual high‐throughput screening pipeline was proposed that can supplement current efforts to find inhibitors. The first iteration identified 11 compounds to test with 3 active for a hit‐rate of 27.3%. The second iteration of the pipeline identified another 11 compounds to test with 7 active for a hit‐rate of 63.6%. © 2018 American Institute of Chemical Engineers Biotechnol. Prog ., 34:1553–1565, 2018