This title appears in the Scientific Report :
2019
Please use the identifier:
http://hdl.handle.net/2128/23195 in citations.
Please use the identifier: http://dx.doi.org/10.1021/acs.jpclett.9b01183 in citations.
Exhaustive Search of Ligand Binding Pathways via Volume-Based Metadynamics
Exhaustive Search of Ligand Binding Pathways via Volume-Based Metadynamics
Determining the complete set of ligands’ binding–unbinding pathways is important for drug discovery and for rational interpretation of mutation data. Here we have developed a metadynamics-based technique that addresses this issue and allows estimating affinities in the presence of multiple escape pa...
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Personal Name(s): | Capelli, Riccardo (Corresponding author) |
---|---|
Carloni, Paolo / Parrinello, Michele | |
Contributing Institute: |
Computational Biomedicine; INM-9 JARA - HPC; JARA-HPC Computational Biomedicine; IAS-5 |
Published in: | The journal of physical chemistry letters, 10 (2019) 12, S. 3495 - 3499 |
Imprint: |
Washington, DC
ACS
2019
|
PubMed ID: |
31188006 |
DOI: |
10.1021/acs.jpclett.9b01183 |
Document Type: |
Journal Article |
Research Program: |
HPC-aided design of drugs with improved kinetics of binding Human Brain Project Specific Grant Agreement 2 Theory, modelling and simulation |
Link: |
Published on 2019-06-03. Available in OpenAccess from 2020-06-03. Published on 2019-06-03. Available in OpenAccess from 2020-06-03. Restricted Published on 2019-06-03. Available in OpenAccess from 2020-06-03. Published on 2019-06-03. Available in OpenAccess from 2020-06-03. Restricted |
Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.1021/acs.jpclett.9b01183 in citations.
Determining the complete set of ligands’ binding–unbinding pathways is important for drug discovery and for rational interpretation of mutation data. Here we have developed a metadynamics-based technique that addresses this issue and allows estimating affinities in the presence of multiple escape pathways. Our approach is shown on a lysozyme T4 variant in complex with a benzene molecule. The calculated binding free energy is in agreement with experimental data. Remarkably, not only were we able to find all the previously identified ligand binding pathways, but also we identified three pathways previously not identified as such. These results were obtained at a small computational cost, making this approach valuable for practical applications, such as screening of small compound libraries. |