Projects per year
Abstract
Kallikrein-8, a serine protease, is a target for structure-based drug design due to its therapeutic potential in treating Alzheimer’s disease and is also useful as a biomarker in ovarian cancer. We present a binding assessment of ligands to kallikrein-8 using a residue-wise decomposition of the binding energy. Binding of four putative inhibitors of kallikrein-8 is investigated through molecular dynamics simulation and ligand binding energy evaluation with two methods (MM/PBSA and WaterSwap). For visualization of the residue-wise decomposition of binding energies, chemical energy-wise decomposition or CHEWD is introduced as a plugin to UCSF Chimera and Pymol. CHEWD allows easy comparison between ligands using individual residue contributions to the binding energy. Molecular dynamics simulations indicate one ligand binds stably to the kallikrein-8 S1 binding site. Comparison with other members of the kallikrein family shows that residues responsible for binding are specific to kallikrein-8. Thus, ZINC02927490 is a promising lead for development of novel kallikrein-8 inhibitors.
Original language | English |
---|---|
Pages (from-to) | 461-475 |
Number of pages | 15 |
Journal | Journal of Computer-Aided Molecular Design |
Volume | 33 |
Issue number | 5 |
Early online date | 15 Apr 2019 |
DOIs | |
Publication status | Published - 15 May 2019 |
Research Groups and Themes
- BrisSynBio
- Bristol BioDesign Institute
Keywords
- synthetic biology
- Binding energy
- Molecular dynamics simulation
- SYNTHETIC BIOLOGY
- Chemical energy-wise decomposition
- WaterSwap
- Kallikrein 8
Fingerprint
Dive into the research topics of 'Visualizing protein–ligand binding with chemical energy-wise decomposition (CHEWD): application to ligand binding in the kallikrein-8 S1 Site'. Together they form a unique fingerprint.Projects
- 4 Finished
-
Link account to CHEM RB1768 (EP/M027546/1) - BristolBridge: Sustained chlorhexidine delivery gels for care of the umbilical cord in developing countries
Barbour , M. E. (Principal Investigator)
1/11/15 → 31/01/16
Project: Research
-
CCP-BioSim: Biomolecular Simulation at the Life Sciences Interface
Mulholland, A. J. (Principal Investigator)
1/07/15 → 30/04/21
Project: Research
-
BrisSynBio: Bristol Centre for Synthetic Biology
Woolfson, D. N. (Principal Investigator)
31/07/14 → 31/03/22
Project: Research
Equipment
-
HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities
Alam, S. R. (Manager), Williams, D. A. G. (Manager), Eccleston, P. E. (Manager) & Greene, D. (Manager)
Facility/equipment: Facility