scholarly journals Applying efficient implicit nongeometric constraints in alchemical free energy simulations

2011 ◽  
Vol 32 (16) ◽  
pp. 3423-3432 ◽  
Author(s):  
Jennifer L. Knight ◽  
Charles L. Brooks
Keyword(s):  
Free Energy ◽  
Energy Simulations ◽  
Alchemical Free Energy

BAR-based optimum adaptive sampling regime for variance minimization in alchemical transformation

2017 ◽  
Vol 19 (23) ◽  
pp. 15005-15020 ◽  
Author(s):  
Zhao X. Sun ◽  
Xiao H. Wang ◽  
John Z. H. Zhang
Keyword(s):  
Free Energy ◽  
Importance Sampling ◽  
Adaptive Sampling ◽  
Variance Minimization ◽  
Sampling Regime ◽  
Energy Simulations ◽  
Alchemical Free Energy

The efficiency of alchemical free energy simulations with a staging strategy is improved by adaptively manipulating the significance of each ensemble followed by importance sampling.

scholarly journals FESetup: Automating Setup for Alchemical Free Energy Simulations

2015 ◽  
Vol 55 (12) ◽  
pp. 2485-2490 ◽  
Author(s):  
Hannes H. Loeffler ◽  
Julien Michel ◽  
Christopher Woods
Keyword(s):  
Free Energy ◽  
Energy Simulations ◽  
Alchemical Free Energy

Chaperoned alchemical free energy simulations: A general method for QM, MM, and QM/MM potentials

2004 ◽  
Vol 120 (20) ◽  
pp. 9450-9453 ◽  
Author(s):  
Wei Yang ◽  
Ryan Bitetti-Putzer ◽  
Martin Karplus
Keyword(s):  
Free Energy ◽  
Energy Simulations ◽  
Alchemical Free Energy ◽  
General Method

Calculation of free energy changes due to mutations from alchemical free energy simulations

2015 ◽  
Vol 14 (03) ◽  
pp. 1550023 ◽  
Author(s):  
M. Harunur Rashid ◽  
Germano Heinzelmann ◽  
Serdar Kuyucak
Keyword(s):  
Free Energy ◽  
Fundamental Problem ◽  
Binding Free Energy ◽  
Computational Design ◽  
Md Simulations ◽  
Binding Mode ◽  
Free Energy Calculations ◽  
Energy Calculations ◽  
Energy Simulations ◽  
Alchemical Free Energy

How a mutation affects the binding free energy of a ligand is a fundamental problem in molecular biology/biochemistry with many applications in pharmacology and biotechnology, e.g. design of drugs and enzymes. Free energy change due to a mutation can be determined most accurately by performing alchemical free energy calculations in molecular dynamics (MD) simulations. Here we discuss the necessary conditions for success of free energy calculations using toxin peptides that bind to ion channels as examples. We show that preservation of the binding mode is an essential requirement but this condition is not always satisfied, especially when the mutation involves a charged residue. Otherwise problems with accuracy of results encountered in mutation of charged residues can be overcome by performing the mutation on the ligand in the binding site and bulk simultaneously and in the same system. The proposed method will be useful in improving the affinity and selectivity profiles of drug leads and enzymes via computational design and protein engineering.

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