title: Effect of artificial periodicity in simulations of biomolecules under Ewald boundary conditions: a continuum electrostatics study.
abstract: Ewald and related methods are nowadays routinely used in explicit-solvent simulations of biomolecules, although they impose an artificial periodicity in systems which are inherently non-periodic. The consequences of this approximation should be assessed, since they may crucially affect the reliability of computer simulations under Ewald boundary conditions. In the present study we use a method based on continuum electrostatics to investigate the nature and magnitude of possible periodicity-induced artifacts on the potentials of mean force for conformational equilibria in biomolecules. Three model systems and pathways are considered: polyalanine oligopeptides (unfolding), a DNA tetranucleotide (separation of the strands), and the protein Sac7d (conformations from a molecular dynamics simulation). Artificial periodicity may significantly affect these conformational equilibria, in each case stabilizing the most compact conformation of the biomolecule. Three factors enhance periodicity-induced artifacts: (i) a solvent of low dielectric permittivity; (ii) a solute size which is non-negligible compared to the size of the unit cell; and (iii) a non-neutral solute. Neither the neutrality of the solute nor the absence of charge pairs at distances exceeding half the edge of the unit cell do guarantee the absence of artifacts.
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla 92093-0365, USA. phunenbe@ucsd.edu
authors.forename: P H
authors.initials: PH
authors.lastname: Hünenberger
authors.forename: J A
authors.initials: JA
authors.lastname: McCammon
mesh_terms: D000465:Algorithms; D001426:Bacterial Proteins / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry; D011073:Polyamines / Q000737:chemistry; D011487:Protein Conformation; D012997:Solvents
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D009841:Oligonucleotides; D009842:Oligopeptides; D011073:Polyamines; D012997:Solvents