Yuan, Chenhui and Koes, David
(2014)
Computing free energies with PyBrella.
In: 19th Annual International Conference on Research in Computational Molecular Biology (RECOMB) 2015, 11 April 2015 - 15 April 2015, Warsaw, Poland.
Abstract
Calculations of the rates of disassociation between small molecules and proteins have numerous applications, including assisting rapid discovery and testing of novel drugs. Free energy calculations consider the enthalpy and entropy of the full protein-ligand-water system and so have the potential to be more accurate than faster, single-point calculations. In this study, methods are explored to predict the binding affinity of various molecules to proteins by molecular dynamics and umbrella sampling. An attempt was made to determine the potential of mean force (PMF) for the molecule, which was compared to its known binding capability. Factors including simulation resources, amounts of sampling, force strength parameters, and correlation between predicted energy and actual rate constants were considered in order to evaluate the umbrella sampling methods. Limitations in the simulation environment, such as the scaling of the PMF for sampling, biases in the SMD trajectory, and variations between ligands, were also investigated in the hope of creating a more comprehensive approach for predicting the target-molecule interaction.
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Details
| Item Type: |
Conference or Workshop Item
(Poster)
|
| Status: |
Published |
| Creators/Authors: |
|
| Date: |
20 May 2014 |
| Date Type: |
Publication |
| Journal or Publication Title: |
F1000 Research |
| Publisher: |
F1000 Research Ltd. |
| Event Title: |
19th Annual International Conference on Research in Computational Molecular Biology (RECOMB) 2015 |
| Event Dates: |
11 April 2015 - 15 April 2015 |
| Event Type: |
Conference |
| Schools and Programs: |
School of Medicine > Computational and Systems Biology |
| Refereed: |
No |
| ISSN: |
2046-1402 |
| Official URL: |
https://f1000research.com/posters/1095479 |
| Additional Information: |
Funding: National Institutes of Health (NIH), GM108340-01 Competing Interests: No competing interests were disclosed |
| Date Deposited: |
22 Nov 2016 17:45 |
| Last Modified: |
25 Aug 2017 04:56 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/30143 |
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