Balancing Accuracy and Cost of Confinement Simulations by Interpolation and Extrapolation of Confinement Energies.
Improvements to the confinement method for the calculation of conformational free energy differences are presented. By taking advantage of phase space overlap between simulations at different frequencies, significant gains in accuracy and speed are reached. The optimal frequency spacing for the simulations is obtained from extrapolations of the confinement energy, and relaxation time analysis is used to determine time steps, simulation lengths, and friction coefficients. At postprocessing, interpolation of confinement energies is used to significantly reduce discretization errors in the calculation of conformational free energies. The efficiency of this protocol is illustrated by applications to alanine n-peptides and lactoferricin. For the alanine-n-peptide, errors were reduced between 2- and 10-fold and sampling times between 8- and 67-fold, while for lactoferricin the long sampling times at low frequencies were reduced 10-100-fold.
Department of Chemistry, University of South Florida , 4202 East Fowler Avenue, CHE 205, Tampa, Florida 33620, United States.
François
F
Villemot
Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche , Via Mario Bianco 9, 20131 Milano, Italy.|Dipartimento di Fisica, Università degli Studi di Milano and INFN , Via Celoria 16, 20133 Milano, Italy.
Riccardo
R
Capelli
Istituto di Chimica del Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche , Via Mario Bianco 9, 20131 Milano, Italy.
Giorgio
G
Colombo
Department of Chemistry, University of South Florida , 4202 East Fowler Avenue, CHE 205, Tampa, Florida 33620, United States.
Arjan
A
van der Vaart
D000409:Alanine / Q000737:chemistry; D007781:Lactoferrin / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
D010455:Peptides; C082171:lactoferricin B; D007781:Lactoferrin; D000409:Alanine