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Adaptive Multilevel Splitting Method for Molecular Dynamics Calculation of Benzamidine-Trypsin Dissociation Time
- Source :
- Journal of Chemical Theory and Computation, Journal of Chemical Theory and Computation, 2016, 12 (6), pp.2983-2989. ⟨10.1021/acs.jctc.6b00277⟩, Journal of Chemical Theory and Computation, American Chemical Society, 2016, 12 (6), pp.2983-2989. ⟨10.1021/acs.jctc.6b00277⟩
- Publication Year :
- 2016
- Publisher :
- HAL CCSD, 2016.
-
Abstract
- International audience Adaptive multilevel splitting (AMS) is a rare event sampling method that requires minimal parameter tuning and allows unbiased sampling of transition pathways of a given rare event. Previous simulation studies have verified the efficiency and accuracy of AMS in the calculation of transition times for simple systems in both Monte Carlo and molecular dynamics (MD) simulations. Now, AMS is applied for the first time to an MD simulation of protein–ligand dissociation, representing a leap in complexity from the previous test cases. Of interest is the dissociation rate, which is typically too low to be accessible to conventional MD. The present study joins other recent efforts to develop advanced sampling techniques in MD to calculate dissociation rates, which are gaining importance in the pharmaceutical field as indicators of drug efficacy. The system investigated here, benzamidine bound to trypsin, is an example common to many of these efforts. The AMS estimate of the dissociation rate was found to be (2.6 ± 2.4) × 102 s–1, which compares well with the experimental value.
- Subjects :
- 0301 basic medicine
Field (physics)
Computer science
Monte Carlo method
Molecular Dynamics Simulation
Ligands
01 natural sciences
Article
Dissociation (chemistry)
Benzamidine
03 medical and health sciences
Search engine
Molecular dynamics
chemistry.chemical_compound
0103 physical sciences
Trypsin
Rare Event Sampling
Statistical physics
Physical and Theoretical Chemistry
Simulation
010304 chemical physics
Sampling (statistics)
Benzamidines
Computer Science Applications
030104 developmental biology
chemistry
Monte Carlo Method
Algorithms
[MATH.MATH-NA]Mathematics [math]/Numerical Analysis [math.NA]
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 15499618 and 15499626
- Database :
- OpenAIRE
- Journal :
- Journal of Chemical Theory and Computation, Journal of Chemical Theory and Computation, 2016, 12 (6), pp.2983-2989. ⟨10.1021/acs.jctc.6b00277⟩, Journal of Chemical Theory and Computation, American Chemical Society, 2016, 12 (6), pp.2983-2989. ⟨10.1021/acs.jctc.6b00277⟩
- Accession number :
- edsair.doi.dedup.....619df35739b846654972221710afd9dd
- Full Text :
- https://doi.org/10.1021/acs.jctc.6b00277⟩