scholarly journals Comparison of Free-Energy Methods to Calculate the Barriers for the Nucleophilic Substitution of Alkyl Halides by Hydroxide

2020 ◽  
Vol 124 (31) ◽  
pp. 6835-6842
Author(s):  
Hafiz Saqib Ali ◽  
Jonathan Higham ◽  
Sam P. de Visser ◽  
Richard H. Henchman
Keyword(s):  
Free Energy ◽  
Nucleophilic Substitution ◽  
Alkyl Halides ◽  
Energy Methods

scholarly journals Novel Directions in Free Energy Methods and Applications

2020 ◽  
Vol 60 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Kira A. Armacost ◽  
Sereina Riniker ◽  
Zoe Cournia
Keyword(s):  
Free Energy ◽  
Energy Methods

scholarly journals How quickly can we predict trimethoprim resistance using alchemical free energy methods?

2020 ◽  
Vol 10 (6) ◽  
pp. 20190141
Author(s):  
Philip W. Fowler
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Dynamics Simulations ◽  
Clinical Microbiology ◽  
Binding Free Energy ◽  
Single Mutation ◽  
Energy Methods ◽  
Synonymous Mutations ◽  
Dynamics Simulations ◽  
Alchemical Free Energy

The emergence of antimicrobial resistance threatens modern medicine and necessitates more personalized treatment of bacterial infections. Sequencing the whole genome of the pathogen(s) in a clinical sample offers one way to improve clinical microbiology diagnostic services, and has already been adopted for tuberculosis in some countries. A key weakness of a genetics clinical microbiology is it cannot return a result for rare or novel genetic variants and therefore predictive methods are required. Non-synonymous mutations in the S. aureus dfrB gene can be successfully classified as either conferring resistance (or not) by calculating their effect on the binding free energy of the antibiotic, trimethoprim. The underlying approach, alchemical free energy methods, requires large numbers of molecular dynamics simulations to be run. We show that a large number ( N = 15) of binding free energies calculated from a series of very short (50 ps) molecular dynamics simulations are able to satisfactorily classify all seven mutations in our clinically derived testset. A result for a single mutation could therefore be returned in less than an hour, thereby demonstrating that this or similar methods are now sufficiently fast and reproducible for clinical use.

scholarly journals Free energy methods in coupled electron ion Monte Carlo

2011 ◽  
Vol 109 (23-24) ◽  
pp. 3029-3036 ◽  
Author(s):  
Elisa Liberatore ◽  
Miguel A. Morales ◽  
David M. Ceperley ◽  
Carlo Pierleoni
Keyword(s):  
Monte Carlo ◽  
Free Energy ◽  
Energy Methods
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