| Autor: |
Makeneni S; Complex Carbohydrate Research Center , University of Georgia , 315 Riverbend Road , Athens , Georgia 30602 , United States., Thieker DF; Complex Carbohydrate Research Center , University of Georgia , 315 Riverbend Road , Athens , Georgia 30602 , United States., Woods RJ; Complex Carbohydrate Research Center , University of Georgia , 315 Riverbend Road , Athens , Georgia 30602 , United States. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of chemical information and modeling [J Chem Inf Model] 2018 Mar 26; Vol. 58 (3), pp. 605-614. Date of Electronic Publication: 2018 Mar 09. |
| DOI: |
10.1021/acs.jcim.7b00588 |
| Abstrakt: |
In this work, we developed a computational protocol that employs multiple molecular docking experiments, followed by pose clustering, molecular dynamic simulations (10 ns), and energy rescoring to produce reliable 3D models of antibody-carbohydrate complexes. The protocol was applied to 10 antibody-carbohydrate co-complexes and three unliganded (apo) antibodies. Pose clustering significantly reduced the number of potential poses. For each system, 15 or fewer clusters out of 100 initial poses were generated and chosen for further analysis. Molecular dynamics (MD) simulations allowed the docked poses to either converge or disperse, and rescoring increased the likelihood that the best-ranked pose was an acceptable pose. This approach is amenable to automation and can be a valuable aid in determining the structure of antibody-carbohydrate complexes provided there is no major side chain rearrangement or backbone conformational change in the H3 loop of the CDR regions. Further, the basic protocol of docking a small ligand to a known binding site, clustering the results, and performing MD with a suitable force field is applicable to any protein ligand system. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
