title: Membrane Protein Properties Revealed through Data-Rich Electrostatics Calculations.
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.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA.
authors.forename: Frank V
authors.initials: FV
authors.lastname: Marcoline
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA; Integrative Program in Quantitative Biology, University of California, San Francisco, CA 94158, USA.
authors.forename: Neville
authors.initials: N
authors.lastname: Bethel
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Guerriero
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Brodsky
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA. Electronic address: michael.grabe@ucsf.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Grabe
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry*; D020816:Amino Acid Motifs; D057225:Data Mining; D006801:Humans; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D016415:Sequence Alignment; D015222:Sodium Channels / Q000737:chemistry*; D012984:Software; D055672:Static Electricity; D040681:Structural Homology, Protein; D050916:TRPV Cation Channels / Q000737:chemistry*; D013816:Thermodynamics; D050995:Voltage-Dependent Anion Channel 1 / Q000737:chemistry*
chemical_list: D018528:ATP-Binding Cassette Transporters; C489277:STE6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015222:Sodium Channels; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C494762:VDAC1 protein, human; D050995:Voltage-Dependent Anion Channel 1