Continuum electrostatic approach for evaluating positions and interactions of proteins in a bilayer membrane

Supunyabut, Chirayut; Fuklang, Sunit; Sompornpisut, Pornthep

doi:10.1016/j.jmgm.2015.04.003

Cited by 6 publications

(7 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prior to building the protein−lipid systems, the initial orientation of R1attached VSD in the membrane was the same as the optimal spatial position of unlabeled KvAP-VSD published previously. 17 In brief, the orientation of the VSD within the membrane was evaluated by calculating the solvation energy with the Poisson−Boltzmann solvent continuum approach. We computed the difference in electrostatic solvation energies of the protein in implicit water and membrane at various positions using the programs APBS and APBSmem.…”

Section: ■ Methodsmentioning

confidence: 99%

“…Prior to building the protein–lipid systems, the initial orientation of R1-attached VSD in the membrane was the same as the optimal spatial position of unlabeled KvAP-VSD published previously . In brief, the orientation of the VSD within the membrane was evaluated by calculating the solvation energy with the Poisson–Boltzmann solvent continuum approach.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Dynamics and Environmental Characteristics of Spin Labels in a KvAP Voltage Sensor by Molecular Dynamics Simulations

2021

Self Cite

View full text Add to dashboard Cite

The nitroxide spin label is the most widely used probe for electron paramagnetic resonance (EPR) spectroscopy studies of the structure and function of biomolecules. However, the role of surrounding environments in determining the dynamics of nitroxide spin labels in biological complex systems remains to be clarified. This study aims to characterize the dynamics and environmental structure of spin labels in the voltage-sensing domain (VSD) of a KvAP potassium channel by means of molecular dynamics (MD) studies. MD simulations for unlabeled and 132 spin-labeled KvAP-VSD models (spin labels introduced at positions 20–151) were carried out in a phospholipid bilayer to evaluate conformational dynamics of nitroxide spin-label side chains in the VSD. Structural flexibility, conformational freedom, and orientation of the spin-label side chains were investigated in relation to their dynamics in different microenvironments. The analysis of MD data showed that the attached spin-label probe did not severely perturb the protein dynamics. The conformational freedoms of the nitroxide side chain vary with the physical structure of the surrounding environments. The two terminal dihedral angles of the nitroxide side chain tend to cluster and adopt several preferred rotameric states. From the nearest-neighbor analysis, the spin label can be exposed to either a homogeneous or heterogeneous environment with various exposure scenarios. The dynamical movement of KvAP-VSD is high at a water-exposed site, moderate in the membrane, and low in the protein core. Understanding the structure and dynamics behaviors of spin labels helps to manage the experimental uncertainty and avoid misleading interpretation in relation to the protein structure.

show abstract

Section: ■ Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Dynamics and Environmental Characteristics of Spin Labels in a KvAP Voltage Sensor by Molecular Dynamics Simulations

2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…The protein structure quality was subsequently validated by the program PROCHECK . Prior to insertion of the protein into an explicit membrane environment, the optimal spatial position of the protein in membranes was determined using the calculation of the electrostatic solvation free energy approach previously described . In brief, all the missing hydrogen atoms were added to the protein structure using the program PDB2PQR. , Partial atomic charges and radii of the protein were taken from the PARSE parameter sets .…”

Section: Methodsmentioning

confidence: 99%

Effect of Ionization State on Voltage-Sensor Structure in Resting State of the Hv1 Channel

Boonamnaj

Sompornpisut

2019

J. Phys. Chem. B

Self Cite

View full text Add to dashboard Cite

Voltage-gated proton-selective channels (Hv1) mediate proton extrusion during intracellular acidification. Hv1 is gated by the proton electrochemical gradient. Intracellular ionizable residues in Hv1 have been proposed to serve as proton-binding sites for pH-dependent gating, but detailed descriptions remain unclear. Here, molecular dynamics (MD) simulations were performed to investigate the effect of ionization states of charged residues on the X-ray structure of Hv1. Modification of the protonation state of acidic residues affected the resting conformation of Hv1 by disrupting salt bridges between S4 and the other segments. Upon protonation, conformational changes enabled the displacement of the S4 arginines toward the extracellular side and increased the mobility of hydrophobic residues at the gate. The aqueous crevice was considerably wider with increased hydration in the pore. Solvation free energies of the pore residues were low at the extra- and intracellular entrances, whereas the narrowest region exhibited the energy barrier for water translocation. Our MD data showed that water molecules in the upper and lower pore oriented differently. In neutral pH, the pore water oriented its dipole pointing away from the voltage-sensing domain center, whereas the opposite direction of the water dipole was observed in acidic pH.

show abstract

“…The combined model of mHv1cc-VSD/hHv1-CTD (Figure S1C) and the truncated C-terminal domain model in the dimer form were built using visual molecular dynamics (VMD) . The favorable position of protein in the lipid bilayer was carefully predicted by a method previously developed, using the adaptive Poisson–Boltzmann solver (APBS) software package, with PARSE partial charges . The hydrogen atoms and atomic charges were assigned with the PDB2PQR program. , …”

Section: Methodsmentioning

confidence: 99%

Insight into the Role of the Hv1 C-Terminal Domain in Dimer Stabilization

Boonamnaj

Sompornpisut

2018

J. Phys. Chem. B

Self Cite

View full text Add to dashboard Cite

The voltage-gated proton-selective channel (Hv1) conducts protons in response to changes in membrane potential. The Hv1 protein forms dimers in the membrane. Crystal structures of Hv1 channels have revealed that the primary contacts between the two monomers are in the C-terminal domain (CTD), which forms a coiled-coil structure. The role of Hv1-CTD in channel assembly and activity is not fully understood. Here, molecular dynamics (MD) simulations of full-length and truncated CTD models of human and mouse Hv1 channels reveal a strong contribution of the CTD to the packing of the transmembrane domains. Simulations of the CTD models highlight four fundamental interactions of the key residues contributing to dimer stability. These include salt bridges, hydrophobic interactions, hydrogen bonds, and a disulfide bond across the dimer interface. At neutral pH, salt-bridge interactions increase dimer stability and the dimer becomes less stable at acidic pH. Hydrophobic core packing of the heptad pattern is important for stability, as shown by favorable nonpolar binding free energies rather than by electrostatic components. Moreover, free-energy calculations indicate that a more uniform hydrophobic core in the coiled-coil structure of the Hv1-NIN, a channel carrying the triple mutation M234N-N235I-V236N, leads to an increase in dimer stability with respect to the wild-type. A Cys disulfide bond has a strong impact on dimer stability by holding the dimer together and facilitating the interactions described above. These results are consistent with dissociative temperatures and energy barriers of dimer dissociation obtained from the temperature-accelerated MD.

show abstract

Continuum electrostatic approach for evaluating positions and interactions of proteins in a bilayer membrane

Cited by 6 publications

References 63 publications

Dynamics and Environmental Characteristics of Spin Labels in a KvAP Voltage Sensor by Molecular Dynamics Simulations

Dynamics and Environmental Characteristics of Spin Labels in a KvAP Voltage Sensor by Molecular Dynamics Simulations

Effect of Ionization State on Voltage-Sensor Structure in Resting State of the Hv1 Channel

Insight into the Role of the Hv1 C-Terminal Domain in Dimer Stabilization

Contact Info

Product

Resources

About