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Minimum MD simulation length required to achieve reliable results in free energy perturbation calculations: Case study of relative binding free energies of fructose‐1,6‐bisphosphatase inhibitors
Author(s) -
Rathore R.S.,
Aparoy P.,
Reddanna P.,
Kondapi A. K.,
Rami Reddy M.
Publication year - 2011
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.21791
Subject(s) - benchmark (surveying) , free energy perturbation , solvation , convergence (economics) , yardstick , perturbation theory (quantum mechanics) , ab initio , computer science , perturbation (astronomy) , energy (signal processing) , chemistry , statistical physics , computational chemistry , molecular dynamics , mathematics , physics , ion , quantum mechanics , geodesy , organic chemistry , economic growth , economics , geography
In an attempt to establish the criteria for the length of simulation to achieve the desired convergence of free energy calculations, two studies were carried out on chosen complexes of FBPase‐AMP mimics. Calculations were performed for varied length of simulations and for different starting configurations using both conventional‐ and QM/MM‐FEP methods. The results demonstrate that for small perturbations, 1248 ps simulation time could be regarded a reasonable yardstick to achieve convergence of the results. As the simulation time is extended, the errors associated with free energy calculations also gradually tapers off. Moreover, when starting the simulation from different initial configurations of the systems, the results are not changed significantly, when performed for 1248 ps. This study carried on FBPase‐AMP mimics corroborates well with our previous successful demonstration of requirement of simulation time for solvation studies, both by conventional and ab initio FEP. The establishment of aforementioned criteria of simulation length serves a useful benchmark in drug design efforts using FEP methodologies, to draw a meaningful and unequivocal conclusion. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011