Optimal bond-constraint topology for molecular dynamics simulations of cholesterol

18 October 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

We recently observed artificial temperature gradients in molecular dynamics (MD) simulations of phase separating ternary lipid mixtures using the Martini 2 force field. We traced this artifact to insufficiently converged bond length constraints with typical time steps and default settings for the linear constraint solver (LINCS). Here, we systematically optimize the constraint scaffold of cholesterol. With massive virtual sites in an equimomental arrangement, we accelerate bond constraint convergence while preserving the original cholesterol force field and dynamics. The optimized model does not induce nonphysical temperature gradients even at relaxed LINCS settings and is at least as fast as the original model at the strict LINCS settings required for proper thermal sampling. Furthermore, we provide a python script to diagnose possible problems with constraint convergence also for other molecules and force fields. Equimomental constraint topology optimization can also be used to boost constraint convergence in atomistic MD simulations of molecular systems.

Keywords

Molecular Dynamics
Lipid phase separation
Cholesterol
LINCS
equimomenal systems
MARTINI
CHARMM

Supplementary materials

Title
Description
Actions
Title
Optimal bond-constraint topology for molecular dynamics simulations of cholesterol - SI
Description
Supporting information for Optimal bond-constraint topology for molecular dynamics simulations of cholesterol
Actions

Supplementary weblinks

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.