A Continuum Poisson-Boltzmann Model for Membrane Channel Proteins

Li Xiao, Jianxiong Diao, D'Artagnan Greene, Junmei Wang, Ray Luo

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Membrane proteins constitute a large portion of the human proteome and perform a variety of important functions as membrane receptors, transport proteins, enzymes, signaling proteins, and more. Computational studies of membrane proteins are usually much more complicated than those of globular proteins. Here, we propose a new continuum model for Poisson-Boltzmann calculations of membrane channel proteins. Major improvements over the existing continuum slab model are as follows: (1) The location and thickness of the slab model are fine-tuned based on explicit-solvent MD simulations. (2) The highly different accessibilities in the membrane and water regions are addressed with a two-step, two-probe grid-labeling procedure. (3) The water pores/channels are automatically identified. The new continuum membrane model is optimized (by adjusting the membrane probe, as well as the slab thickness and center) to best reproduce the distributions of buried water molecules in the membrane region as sampled in explicit water simulations. Our optimization also shows that the widely adopted water probe of 1.4 Å for globular proteins is a very reasonable default value for membrane protein simulations. It gives the best compromise in reproducing the explicit water distributions in membrane channel proteins, at least in the water accessible pore/channel regions. Finally, we validate the new membrane model by carrying out binding affinity calculations for a potassium channel, and we observe good agreement with the experimental results.

Original languageEnglish (US)
Pages (from-to)3398-3412
Number of pages15
JournalJournal of Chemical Theory and Computation
Volume13
Issue number7
DOIs
StatePublished - Jul 11 2017

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Ion Channels
membranes
continuums
proteins
Proteins
Membranes
Water
Membrane Proteins
water
slabs
Potassium Channels
probes
Proteome
proteome
Labeling
porosity
Carrier Proteins
simulation
Molecules
marking

ASJC Scopus subject areas

  • Computer Science Applications
  • Physical and Theoretical Chemistry

Cite this

A Continuum Poisson-Boltzmann Model for Membrane Channel Proteins. / Xiao, Li; Diao, Jianxiong; Greene, D'Artagnan; Wang, Junmei; Luo, Ray.

In: Journal of Chemical Theory and Computation, Vol. 13, No. 7, 11.07.2017, p. 3398-3412.

Research output: Contribution to journalArticle

Xiao, Li ; Diao, Jianxiong ; Greene, D'Artagnan ; Wang, Junmei ; Luo, Ray. / A Continuum Poisson-Boltzmann Model for Membrane Channel Proteins. In: Journal of Chemical Theory and Computation. 2017 ; Vol. 13, No. 7. pp. 3398-3412.
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