
Professor
Cardiovascular Research Institute
Email
+1 415 502-2874
Education and Training
07/2021
University of California, San Francisco
Diversity, Equity, and Inclusion Champion Training
Diversity, Equity, and Inclusion Champion Training
07/2021
University of California, San Francisco
Diversity, Equity, and Inclusion Champion Training
Diversity, Equity, and Inclusion Champion Training
Research Activities And Funding
Jan 1, 2021 - Nov 30, 2024
Ion permeation, lipid flipping, and membrane remodeling by TMEM16 proteins
NIH R01GM137109
Role: Principal Investigator
NIH R01GM137109
Role: Principal Investigator
Sep 1, 2012 - Jul 31, 2015
Computer simulations of lysosomal and osteoclast microphysiology
NIH R21GM100224
Role: Principal Investigator
NIH R21GM100224
Role: Principal Investigator
Websites
ORCID
0000-0003-3509-5997 Additional info
Faculty Type
Core CVRI Faculty
Research Summary:
Our lab uses computational methods to understand biological phenomena. We are primarily interested in the mechanical operation of ion channels and transporters, which move ions and small molecules across membranes. Additionally, we use theoretical approaches to explore how these membrane proteins work together to regulate ion homeostasis in organelles such as the lysosome and Golgi. Lastly, we are developing methodologies for predicting the stability of membrane proteins to understand how mutations give rise to a loss of function, improper trafficking or degradation.
Publications
Detection of Cytosolic Ion Concentrations by the Trans-Golgi Network/Early Endosome is Important for Salt Tolerance.
bioRxiv : the preprint server for biology
Author Correction: Structure of the human K2P13.1 channel reveals a hydrophilic pore restriction and lipid cofactor site.
Nature structural & molecular biology
A cell-based scrambling assay reveals phospholipid headgroup preference of TMEM16F on the plasma membrane.
bioRxiv : the preprint server for biology
Substrate recognition and allosteric regulation of synaptic vesicle glutamate transporter VGLUT2.
Nature structural & molecular biology
Deep learning-guided design of dynamic proteins.
Science (New York, N.Y.)
Robust lipid scrambling by TMEM16 proteins requires an open groove and thin membrane.
bioRxiv : the preprint server for biology
Structure of the human K2P13.1 channel reveals a hydrophilic pore restriction and lipid cofactor site.
Nature structural & molecular biology
Coupled equilibria of dimerization and lipid binding modulate SARS Cov 2 Orf9b interactions and interferon response.
bioRxiv : the preprint server for biology
A Cooperative Model for Symmetric Ligand Binding to Protein Fibrils.
bioRxiv : the preprint server for biology
Structure of the human K2P13.1(THIK-1) channel reveals a novel hydrophilic pore restriction and lipid cofactor site.
bioRxiv : the preprint server for biology
Membrane potential accelerates sugar uptake by stabilizing the outward facing conformation of the Na/glucose symporter vSGLT.
Nature communications
Brominated lipid probes expose structural asymmetries in constricted membranes.
Nature structural & molecular biology
Quaternary structure independent folding of voltage-gated ion channel pore domain subunits.
Nature structural & molecular biology
Berkeley Madonna Version 10-A simulation package for solving mathematical models.
CPT: pharmacometrics & systems pharmacology
Taking the Monte-Carlo gamble: How not to buckle under the pressure!
Journal of computational chemistry
Elucidation of the molecular interactions that enable stable assembly and structural diversity in multicomponent immune receptors.
Proceedings of the National Academy of Sciences of the United States of America
Inroads into Membrane Physiology through Transport Nanomachines.
Journal of molecular biology
Allosteric cooperation in a de novo-designed two-domain protein.
Proceedings of the National Academy of Sciences of the United States of America
K2P channel C-type gating involves asymmetric selectivity filter order-disorder transitions.
Science advances
A Computational Model of Protein Induced Membrane Morphology with Geodesic Curvature Driven Protein-Membrane Interface.
Journal of computational physics
A kinetic mechanism for enhanced selectivity of membrane transport.
PLoS computational biology
A systems-biology approach to molecular machines: Exploration of alternative transporter mechanisms.
PLoS computational biology
EmrE reminds us to expect the unexpected in membrane transport.
The Journal of general physiology
Protons in small spaces: Discrete simulations of vesicle acidification.
PLoS computational biology
Biophysics at the coffee shop: lessons learned working with George Oster.
Molecular biology of the cell
Harmonizing Experimental Data with Modeling to Predict Membrane Protein Insertion in Yeast.
Biophysical Journal
A multiscale model of mechanotransduction by the ankyrin chains of the NOMPC channel.
The Journal of general physiology
Chemically induced vesiculation as a platform for studying TMEM16F activity.
Proceedings of the National Academy of Sciences of the United States of America
Inhibitor binding mode and allosteric regulation of Na+-glucose symporters.
Nature communications
Cilia-Associated Oxysterols Activate Smoothened.
Molecular cell
Substrate-bound outward-open structure of a Na+-coupled sialic acid symporter reveals a new Na+ site.
Nature communications
Conformational transitions of the sodium-dependent sugar transporter, vSGLT.
Proceedings of the National Academy of Sciences of the United States of America
Protonation state of glutamate 73 regulates the formation of a specific dimeric association of mVDAC1.
Proceedings of the National Academy of Sciences of the United States of America
Transmembrane helix hydrophobicity is an energetic barrier during the retrotranslocation of integral membrane ERAD substrates.
Molecular biology of the cell
New Continuum Approaches for Determining Protein-Induced Membrane Deformations.
Biophysical Journal
Atomistic insight into lipid translocation by a TMEM16 scramblase.
Proceedings of the National Academy of Sciences of the United States of America
Stochastic steps in secondary active sugar transport.
Proceedings of the National Academy of Sciences of the United States of America
Direct observation of proton pumping by a eukaryotic P-type ATPase.
Science (New York, N.Y.)
Continuum descriptions of membranes and their interaction with proteins: Towards chemically accurate models.
Biochimica et biophysica acta
Membrane Protein Properties Revealed through Data-Rich Electrostatics Calculations.
Structure (London, England : 1993)
Simulating Current-Voltage Relationships for a Narrow Ion Channel Using the Weighted Ensemble Method.
Journal of chemical theory and computation
WESTPA: an interoperable, highly scalable software package for weighted ensemble simulation and analysis.
Journal of chemical theory and computation
De novo design of a transmembrane Zn²⁺-transporting four-helix bundle.
Science (New York, N.Y.)
Structure-guided simulations illuminate the mechanism of ATP transport through VDAC1.
Nature structural & molecular biology
Continuum approaches to understanding ion and peptide interactions with the membrane.
The Journal of membrane biology
Structural determinants of water permeation through the sodium-galactose transporter vSGLT.
Biophysical Journal
A model of lysosomal pH regulation.
The Journal of general physiology
Simulating rare events using a weighted ensemble-based string method.
The Journal of chemical physics
Membrane bending is critical for the stability of voltage sensor segments in the membrane.
The Journal of general physiology
Simulations of the alternating access mechanism of the sodium symporter Mhp1.
Biophysical Journal
Constraint-based, homology model of the extracellular domain of the epithelial Na+ channel α subunit reveals a mechanism of channel activation by proteases.
The Journal of biological chemistry
Water permeation through the sodium-dependent galactose cotransporter vSGLT.
Biophysical Journal
Characterization of the PCMBS-dependent modification of KCa3.1 channel gating.
The Journal of general physiology
Allosteric inhibition of the epithelial Na+ channel through peptide binding at peripheral finger and thumb domains.
The Journal of biological chemistry
The electrostatics of VDAC: implications for selectivity and gating.
Journal of molecular biology
Conformational dynamics of the inner pore helix of voltage-gated potassium channels.
The Journal of chemical physics
A continuum method for determining membrane protein insertion energies and the problem of charged residues.
The Journal of general physiology
Getting in sync with dimeric Eg5. Initiation and regulation of the processive run.
The Journal of biological chemistry
Electrostatic interactions in the channel cavity as an important determinant of potassium channel selectivity.
Proceedings of the National Academy of Sciences of the United States of America
K+ channel selectivity depends on kinetic as well as thermodynamic factors.
Proceedings of the National Academy of Sciences of the United States of America
Meta-analysis: accuracy of quantitative ultrasound for identifying patients with osteoporosis.
Annals of internal medicine
The S4 voltage sensor packs against the pore domain in the KAT1 voltage-gated potassium channel.
Neuron
A quantitative assessment of models for voltage-dependent gating of ion channels.
Proceedings of the National Academy of Sciences of the United States of America
Electrostatic model of S4 motion in voltage-gated ion channels.
Biophysical Journal
Protein interactions and membrane geometry.
Biophysical Journal
Biosynthesis and secretion of pituitary hormones: dynamics and regulation.
Archives of physiology and biochemistry
Proton leak and CFTR in regulation of Golgi pH in respiratory epithelial cells.
American journal of physiology. Cell physiology
Cystic fibrosis transmembrane conductance regulator and H+ permeability in regulation of Golgi pH.
JOP : Journal of the pancreas
Mechanisms of pH regulation in the regulated secretory pathway.
The Journal of biological chemistry
Regulation of organelle acidity.
The Journal of general physiology
The mechanochemistry of V-ATPase proton pumps.
Biophysical Journal
How Fo-ATPase generates rotary torque.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Energy transduction in the sodium F-ATPase of Propionigenium modestum.
Proceedings of the National Academy of Sciences of the United States of America
Pathways, pathway tubes, pathway docking, and propagators in electron transfer proteins.
Journal of bioenergetics and biomembranes
Address
555 & 535 Mission Bay Blvd Sou, Rm 452T
UCSF Box 3122
San Francisco, CA 94158
United States