Cutoff size does strongly influence molecular dynamics results on solvated polypeptides

Abstract

The behavior of a 17-residue model peptide is analyzed by means of molecular dynamics simulations including explicitly more than a thousand water molecules. On the basis of the charge-group concept, Coulomb interactions are truncated for three values of the cutoff radius: 0.6, 1.0, and 1.4 nm. It is found that the stability of an alpha-helix, which acts as a common starting configuration, is a function of the cutoff size. While the overall stability of the helix is conserved in a simulation using a cutoff of 1.0 nm, it is lost within a very short period of 100 ps when the cutoff is increased to 1.4 nm. This demonstrates that the commonly used cutoff size of 1.0 nm is inappropriate because it does not ensure the convergence of Coulomb interactions. In order to permit an independent judgment, we have performed a 225-ps simulation using the Ewald summation technique, which is more elaborate but circumvents the problem to find an appropriate cutoff value. In contrast to the 1.4-nm cutoff trajectory, the Ewald technique simulation conserves the helical character of the peptide conformation. This demonstrates that even 1.4 nm is too short a cutoff. Due to the fundamental uncertainty introduced by the use of a simple cutoff, this truncation scheme seems questionable for molecular dynamics simulations of solvated biomolecules.

A reoptimization of the five-site water potential (TIP5P) for use with Ewald sums

“…Problems associated with the use of sharp cutoffs and the importance of using Ewald sums has been demonstrated for the simulation of water [19][20][21][22][23][24][25] and ionic solutions, 26 -29 as well as proteins and peptides. [30][31][32][33][34] One general problem introduced by the use of cutoffs is an upward drift in the total energy of the system. 35 Increasingly, the use of Ewald or particle mesh Ewald has become the standard approach and is now included in common molecular simulation packages, including AMBER 36 and CHARMM.…”

Removing systematic errors in interionic potentials of mean force computed in molecular simulations using reaction-field-based electrostatics

“…27 On the conceptual side, shifting and switching do not help the fact that a long-range interaction is replaced by a short-range one, and this has dramatic consequences for simulated systems, as has been well documented in literature. 3,4 The effect of the truncated part of the Coulomb interactions can be approximated using models of continuum electrostatics. By solving Poisson equation for an empty sphere embedded in infinite dielectric continuum of permittivity ⑀, it is possible to find exactly the polarization force acting on a probe charge located at the center of the sphere that is created by a charge at any other point inside the sphere.…”

“…26͒ water under periodic boundary conditions. Three sizes of the boxes were considered, 2.5ϫ 2.5ϫ 4, 3 ϫ 3 ϫ 4, and 4 ϫ 4 ϫ 5 nm 3 . Three different schemes to treat electrostatic interactions were examined ͑i͒ straight cutoffs, ͑ii͒ reaction-field corrections, 7 and ͑iii͒ lattice summation.…”

“…The cutoff based methods are much faster than the lattice sum approaches. 1,2 However, they are generally believed to be considerably less accurate, [3][4][5] although the opinions appear to be split. 6 A third, alternative approach to electrostatics is based on adding corrections to the truncated electrostatic potentials that take into account electric fields created by the polarization of vacuum cavities embedded in continuum dielectric media, or the reaction fields ͑RFs͒.…”

De novo prediction of polypeptide conformations using dihedral probability grid Monte Carlo methodology

“…Goddard I l l , manuscript in prep.). In the latter stages, larger nonbond cutoffs lead to increased structural accuracy (Schreiber & Steinhauser, 1992).…”