Extending the scope of alchemical perturbation methods for ligand binding free energy calculations
(2016) KFK920 20161Biophysical Chemistry
- Abstract (Swedish)
- Previously, a method for computing binding free energies between different poses of a ligand bound to a protein using alchemical perturbation was developed. The methodology is to perturb the ligand into a smaller version, common to both poses, from which the difference in free energy between poses can be computed. Here, the method is further improved by finding low-error setups for the method, by investigating different kinds of restraints put on the system during simulation and different kinds of parameters for the soft-core potential. The best low-error setup found was using a 1-1-48 soft-core potential with a water barrier and positional restraints for all the non-hydrogen atoms in the system. Instability was detected for one of the... (More)
- Previously, a method for computing binding free energies between different poses of a ligand bound to a protein using alchemical perturbation was developed. The methodology is to perturb the ligand into a smaller version, common to both poses, from which the difference in free energy between poses can be computed. Here, the method is further improved by finding low-error setups for the method, by investigating different kinds of restraints put on the system during simulation and different kinds of parameters for the soft-core potential. The best low-error setup found was using a 1-1-48 soft-core potential with a water barrier and positional restraints for all the non-hydrogen atoms in the system. Instability was detected for one of the poses, this was investigated. The key to having a stable pose seems to be to understand the effect on stability of changing the Ryckaert-Bellemans parameters for a single rotatable bond. (Less)
- Popular Abstract (Swedish)
- Det finns utmaningar med datormodeller av läkemedel som binder till proteiner på olika sätt. Genom att göra modellen mer overklig kan osäkerheten i resultatet bli mindre.
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/8895770
- author
- Fagerberg, Eric LU
- supervisor
- organization
- course
- KFK920 20161
- year
- 2016
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- biophysical chemistry, biofysikalisk kemi
- language
- English
- id
- 8895770
- date added to LUP
- 2016-12-16 14:24:01
- date last changed
- 2017-03-03 15:03:47
@misc{8895770, abstract = {{Previously, a method for computing binding free energies between different poses of a ligand bound to a protein using alchemical perturbation was developed. The methodology is to perturb the ligand into a smaller version, common to both poses, from which the difference in free energy between poses can be computed. Here, the method is further improved by finding low-error setups for the method, by investigating different kinds of restraints put on the system during simulation and different kinds of parameters for the soft-core potential. The best low-error setup found was using a 1-1-48 soft-core potential with a water barrier and positional restraints for all the non-hydrogen atoms in the system. Instability was detected for one of the poses, this was investigated. The key to having a stable pose seems to be to understand the effect on stability of changing the Ryckaert-Bellemans parameters for a single rotatable bond.}}, author = {{Fagerberg, Eric}}, language = {{eng}}, note = {{Student Paper}}, title = {{Extending the scope of alchemical perturbation methods for ligand binding free energy calculations}}, year = {{2016}}, }