Molecular docking studies in factor XIa binding site

作者：Balaji Govardhan A; Balaji Vitukudi N; Rao Shashidhar N^*

来源：Journal of Molecular Structure, 2016, 1108: 352-369.

DOI：10.1016/j.molstruc.2015.11.029

• Factor XIa
• Docking
• XP
• SP
• Binding site
• RMSD
• Catalytic aspartate
• Anionic
• GlideScore

Factor XIa inhibitors have been identified to have potential as anticoagulants with robust efficacy and low bleeding risks. In light of their significance and the availability of their 3-D X-ray data in the PDB, we present molecular docking studies carried out with a view to obtain docking protocols that will successfully reproduce the experimentally observed protein-ligand interactions in the case of various X-ray ligands. In this context, we have specifically investigated the efficacy of various cross-docking protocols in reproducing experimental data. Our studies demonstrate that an ensemble of the three apo proteins is capable of accurately docking a majority of the X-ray ligands accurately without invoking any additional conformational flexibility than that present in their experimental structures. Further, we demonstrate that such an ensemble is successfully able to enrich a collection of known active factor XIa inhibitors embedded in a decoy database of drug-like molecules.

• 出版日期2016-3-15