Membrane Protein Properties Revealed through Data-Rich Electrostatics Calculations

Structure. 2015 Aug 4;23(8):1526-1537. doi: 10.1016/j.str.2015.05.014. Epub 2015 Jun 25.

Abstract

The electrostatic properties of membrane proteins often reveal many of their key biophysical characteristics, such as ion channel selectivity and the stability of charged membrane-spanning segments. The Poisson-Boltzmann (PB) equation is the gold standard for calculating protein electrostatics, and the software APBSmem enables the solution of the PB equation in the presence of a membrane. Here, we describe significant advances to APBSmem, including full automation of system setup, per-residue energy decomposition, incorporation of PDB2PQR, calculation of membrane-induced pKa shifts, calculation of non-polar energies, and command-line scripting for large-scale calculations. We highlight these new features with calculations carried out on a number of membrane proteins, including the recently solved structure of the ion channel TRPV1 and a large survey of 1,614 membrane proteins of known structure. This survey provides a comprehensive list of residues with large electrostatic penalties for being embedded in the membrane, potentially revealing interesting functional information.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters / chemistry*
  • Amino Acid Motifs
  • Data Mining
  • Humans
  • Molecular Dynamics Simulation*
  • Molecular Sequence Data
  • Protein Interaction Domains and Motifs
  • Protein Structure, Secondary
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Sequence Alignment
  • Sodium Channels / chemistry*
  • Software*
  • Static Electricity
  • Structural Homology, Protein
  • TRPV Cation Channels / chemistry*
  • Thermodynamics
  • Voltage-Dependent Anion Channel 1 / chemistry*

Substances

  • ATP-Binding Cassette Transporters
  • STE6 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Sodium Channels
  • TRPV Cation Channels
  • TRPV1 protein, human
  • VDAC1 protein, human
  • Voltage-Dependent Anion Channel 1