About

Emad Tajkhorshid is the J. Woodland Hastings Endowed Chair in the Biochemistry Department at the University of Illinois, where he also holds multiple appointments across various colleges including Chemistry, Bioengineering, Pharmacology, Biophysics and Quantitative Biology, Computational Science and Engineering, and the Carle-Illinois College of Medicine. He is a full-time faculty member of the Beckman Institute for Advanced Science and Technology. Since joining the faculty in 2007, he was rapidly promoted to associate professor with tenure in 2010 and then to full professor in 2013. His tenure dossier was recognized as one of the top two tenure cases on the UIUC campus. In 2015, he was named a University of Illinois Scholar, nominated by both UIUC and UIC campuses, and in 2016 he received the Faculty Excellence Award from the School of Molecular and Cellular Biology at UIUC. Later that year, he was appointed Endowed Chair in Biochemistry. Professor Tajkhorshid leads the NIH Center for Macromolecular Modeling and Bioinformatics and the Computational Structural Biology and Molecular Biophysics Group at the Beckman Institute. His research focuses on developing and applying advanced computational techniques to characterize biological phenomena, particularly membranes and membrane proteins, aiming to achieve detailed microscopic views of the structural and dynamical bases underlying biological function. His extensive research portfolio, continuously supported by multiple federal agencies including NIH, NSF, DOE, and DOD, includes mechanistic studies of membrane transport proteins, principles of energy transduction and coupling in bioenergetic proteins, and lipid modulation of protein function, especially in signaling proteins associated with cellular membranes. Dr. Tajkhorshid has authored nearly 300 research articles with an H-index of 78 and over 37,000 citations in high-profile journals such as Nature, Science, Cell, eLife, and PNAS. He has delivered nearly 200 invited lectures internationally and served on editorial boards of major journals including Biophysical Journal, Journal of Biological Chemistry, PLoS Computational Biology, and Biochemical and Biophysical Research Communication. His educational background includes a B.S. from Tehran University (1989), a Ph.D. from the University of Heidelberg (2001), and postdoctoral training at the University of Illinois, Urbana-Champaign (2000-2003).

Research topics

• Chemistry
• Biochemistry
• Biology
• Biophysics
• Computer Science
• Cell biology
• Data Mining
• Crystallography
• Genetics
• Computational chemistry
• Physics
• Polymer chemistry
• Mathematics
• Neuroscience
• Algorithm
• Engineering
• Parallel computing
• Operating system
• Immunology
• Computational biology
• Pathology
• Computational science
• Materials science
• Organic chemistry

Selected publications

• Structure and Mechanism of a Two-component Lanthipeptide Toxin

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-14

  articleOpen access

  Abstract The enterococcal cytolysin is a two-component lanthipeptide natural product that co-operatively kills mammalian cells and bacteria. It is a virulence factor in typically commensal strains of gut-dwelling Enterococcus faecalis and causes a fatal form of alcoholic hepatitis. Despite its clinical significance, little is known about the mechanism of action. We present here the molecular details of cytolysin’s remarkable bioactivity. A high-resolution cryo-electron microscopy structure revealed highly ordered tubular assemblies comprising the two subunits. We further demonstrate these structures disrupt the membranes of eukaryotic and bacterial cells. These results provide the first high-resolution structure of two distinct lanthipeptides interacting with one another and offer an explanation for the unique bioactivity of the cytolysin toxin.

  PublisherDOI

• Characterization and Computational Engineering of Structural Elements Controlling Gas Permeability in <scp>PIP2</scp> ;1 Aquaporins

  Journal of Computational Chemistry · 2026-04-25

  articleOpen accessSenior authorCorresponding

  across the membrane. The hydrophobic central pore, located at the fourfold symmetry axis of an AQP tetrameric architecture, has been proposed to constitute the most optimal pathway for gas transport, although monomeric water pores can also contribute somewhat to permeation of less hydrophobic species. Here, we report a comparative molecular dynamics (MD) study of gas permeability in a plant AQP and a mammalian AQP1, taking advantage of complementary computational protocols including flooding simulations, umbrella sampling, and implicit ligand sampling. PIP2;1 AQPs, present in plants, are experimentally reported to have lower gas permeability than AQP1, which is present both in plants and animals. Using the spinach PIP2;1 (SoPIP2;1) and bovine AQP1 (bAQP1) as the models, the study unravels the specific structural features controlling the permeability of the central pore to gases. In SoPIP2;1, residue Trp79, which is highly conserved in the plant PIP2;1 family and lines directly the central pore, forms a major constriction region and the main barrier against gas permeation. Notably, the occluding conformation of the four Trp79 residues from the four monomers is stabilized by another conserved residue, Phe207 in the central pore. Sequence and structural comparisons show that both of these residues are replaced by less bulky residues in AQP1, for example, by Leu56 and Ala179, respectively, in bAQP1. The role of Phe207 residues in hindering gas permeation through SoPIP2;1 is confirmed by in silico alanine substitution, which reveals its effect on the local constriction produced by Trp79 residues. Conversely, by mutating Leu56 to tryptophan and Ala179 to phenylalanine in bAQP1, we engineer the protein to a less permeable gas channel.

  PublisherDOI

• Voltage sensor conformations induced by LQTS-associated mutations in hERG potassium channels

  Nature Communications · 2025-08-03 · 4 citations

  articleOpen access

  channels, critical to cardiac rhythm. These sensors respond to membrane potential changes by moving within the transmembrane electric field. Mutations in hERG voltage-sensing arginines, associated with Long-QT syndrome, alter channel gating, though underlying mechanisms remain unclear. Using live-cell fluorescence lifetime imaging microscopy, transition metal FRET, an improved dual stop-codon-mediated strategy for noncanonical amino-acid incorporation, and molecular dynamics simulations, we identify intermediate voltage-sensor conformations induced by neutralizing key arginines in the charge transfer center. Phasor plot analysis of lifetime data reveals multiple voltage-dependent FRET states in these mutants, in contrast to the single high-FRET state observed in controls. These intermediate FRET states reflect distinct conformations of the voltage sensor, corresponding to predicted structures of voltage sensors in molecular dynamics simulations. This study provides insights into cardiac channelopathies, highlighting a structural mechanism that impairs voltage sensing in cardiac arrhythmias.

  PublisherOA PDFDOI

• The String Method with Swarms of Trajectories: A Tutorial for Free-Energy Calculations Along a Zero-Drift Pathway

  The Journal of Physical Chemistry B · 2025-06-27 · 3 citations

  articleOpen access

  The objective of this tutorial is to provide a comprehensive overview of the string method and its usage to determine a detailed transition pathway and the free-energy difference between two conformational states of a system. The computational protocol is illustrated in detail by setting out to calculate the free-energy difference between the C7eq and C7ax conformations of the short, terminally blocked peptide, N–acetyl–N′–methylalaninamide. Starting from a rectilinear transition pathway connecting the two conformations in the backbone-torsional subspace, an optimal zero-drift pathway (ZDP) is determined using the string method with a swarm of trajectories. The free-energy change along this path is then estimated using the path-collective variables (PCV) coordinate in the framework of the adaptive biasing force (ABF) importance-sampling algorithm.

  PublisherOA PDFDOI

• An Orchestrated Interaction Network at the Binding Site of Human SERT Enables the Serotonin Occlusion and Import

  Biochemistry · 2025-07-29

  articleOpen accessSenior authorCorresponding

  Serotonin transporter (SERT) regulates serotonergic signals by reuptaking serotonin from the synaptic clefts back into the presynaptic neurons. The recent resolution of the serotonin-SERT complex in multiple conformational states outlined the complete serotonin import cycle. However, a detailed functional appreciation of SERT also involves deciphering the coupling between global structural changes in the transport cycle to the bound chemicals to be transported. By employing molecular dynamics (MD) simulations and free energy calculations in different ligand binding states, here, we reveal how serotonin binding to SERT initiates the global conformational changes essential for serotonin import. Only when serotonin is bound to the central binding site, wedged between transmembrane helices (TMs) 3 and 8, can the system form an interaction network that bridges the two helical domains of the protein, thereby promoting the closure of an extracellular hydrophobic gate and sealing the bound serotonin. To test the role of this hydrophobic gate closure, we designed a series of nonequilibrium MD simulations to steer the outward-facing ↔ occluded transition with different gating configurations. The difference in nonequilibrium work required to fuel the transition indicates that the transition is more likely to happen when the extracellular gate is closed. The transition is not promoted when the gate is open or when 5-HT moves away from TM3 and TM8 toward an alternate pose. Such a local-global coupling is likely shared by other monoamine transporters considering the conservation of all involved structural elements.

  PublisherOA PDFDOI

• Single-molecule imaging reveals the roles of the membrane-binding motif and the C-terminal domain of RNase E in its localization and diffusion in Escherichia coli

  eLife · 2025-10-24

  articleOpen access

  In Escherichia coli, RNase E, a central enzyme in RNA processing and mRNA degradation, contains a catalytic N-terminal domain (NTD), a membrane-targeting sequence (MTS), and a C-terminal domain (CTD). We investigated how MTS and CTD influence RNase E localization, diffusion, and function. Super-resolution microscopy revealed that ∼93% of RNase E localizes to the inner membrane and exhibits slow diffusion similar to polysomes. Comparing the native amphipathic MTS with a transmembrane motif showed that the MTS confers slower diffusion and stronger membrane binding. The CTD further slows diffusion by increasing mass but unexpectedly weakens membrane association. RNase E mutants with partial cytoplasmic localization displayed enhanced co-transcriptional degradation of lacZ mRNA. These findings indicate that variations in the MTS and the presence of the CTD shape the spatiotemporal organization of RNA processing in bacterial cells, providing mechanistic insight into how RNase E domain architecture influences its cellular function.

  PublisherDOI

• Distinct Interactions of Cannabinol and Its Cytochrome P450-Generated Metabolites with Receptors and Sensory Neurons

  Journal of Medicinal Chemistry · 2025-06-26 · 5 citations

  articleOpen access

  levels in dorsal root ganglia sensory neurons─an effect linked to potential pain relief. These findings lay the groundwork for harnessing CBN and its metabolites in novel pain therapeutics.

  PublisherDOI

• Author response: Roles of the membrane-binding motif and the C-terminal domain of RNase E in localization and diffusion in E. coli

  2025-11-07

  peer-reviewOpen access

  Single-molecule imaging uncovers how distinct membrane-binding motifs and the intrinsically disordered C-terminal domain control RNase E’s membrane association and diffusion, linking structural divergence to RNA-processing dynamics in bacteria.

  PublisherDOI

• Author response: Single-molecule imaging reveals the roles of the membrane-binding motif and the C-terminal domain of RNase E in its localization and diffusion in Escherichia coli

  2025-10-24

  peer-reviewOpen access

  In Escherichia coli, RNase E, a central enzyme in RNA processing and mRNA degradation, contains a catalytic N-terminal domain (NTD), a membrane-targeting sequence (MTS), and a C-terminal domain (CTD). We investigated how MTS and CTD influence RNase E localization, diffusion, and function. Super-resolution microscopy revealed that ∼93% of RNase E localizes to the inner membrane and exhibits slow diffusion similar to polysomes. Comparing the native amphipathic MTS with a transmembrane motif showed that the MTS confers slower diffusion and stronger membrane binding. The CTD further slows diffusion by increasing mass but unexpectedly weakens membrane association. RNase E mutants with partial cytoplasmic localization displayed enhanced co-transcriptional degradation of lacZ mRNA. These findings indicate that variations in the MTS and the presence of the CTD shape the spatiotemporal organization of RNA processing in bacterial cells, providing mechanistic insight into how RNase E domain architecture influences its cellular function.

  PublisherDOI

• Electrochemically Mediated Au–C(sp²) Anchors for Molecular Electronics

  The Journal of Physical Chemistry C · 2025-09-19 · 3 citations

  article

  Terminal anchor groups play a key role in the stability and electronic properties of molecular junctions. Single molecule junctions typically consist of two preinstalled terminal anchors linking organic molecules to metal electrodes. Here, we show that p-terphenyl derivatives containing only a single terminal anchor show conductance features similar to junctions with two preinstalled terminal anchors. A set of p-terphenyl derivatives with one terminal anchor was prepared using automated chemical synthesis and characterized using single molecule electronics experiments, molecular dynamics (MD) simulations, bulk electrochemistry and spectroscopy, and nonequilibrium Green’s function-density functional theory (NEGF-DFT) calculations. Our results show that 4-amino-p-terphenyl (PPP) and related analogs exhibit a well-defined high conductance state that is diminished or absent in other p-terphenyl derivatives lacking a preinstalled amine terminal anchor or fluorine or methyl substitutions at the terminal para position. However, a low conductance state is observed in all amino-p-terphenyl derivatives with one preinstalled anchor due to molecular junctions formed by noncovalent dimeric π–π stacking interactions. The observed high conductance state diminishes upon the addition of reducing agents and is restored upon the addition of an oxidizing agent. Our results suggest that the high conductance state arises due to Au–C(sp2) bond formation facilitated by a single electron oxidation event at the electrode surface. A series of control experiments with different anchor groups shows that primary amines play a key role in forming Au–C bonds for molecular junctions. Overall, these results suggest that Au–C bond formation gives rise to high conductance pathways in organic molecules containing only one preinstalled terminal anchor. Insights from this work can be leveraged in the design of molecular electronic devices, particularly in understanding the mechanisms of molecular binding and junction formation.

  PublisherDOI

Recent grants

• Molecular mechanism of Na+ -coupled HCO3- transporters: transport of CO3= and CO2

  NIH · $2.7M · 2021–2025

• NIH Grant U01GM111251

  NIH · $2.9M · 2020

• NIH Grant R01GM086749

  NIH · $1.5M · 2016

• NIH Grant P41RR005969

  NIH · $6.7M · 2012

• WHOLE CELL SIMULATION

  NIH · $23.5M · 1997–2022

Frequent coauthors

• Klaus Schulten

  104 shared

• Po‐Chao Wen

  University of Illinois Urbana-Champaign

  74 shared

• Shigehiko Hayashi

  Kubota (Japan)

  57 shared

• Shashank Pant

  49 shared

• Sándor Suhai

  German Cancer Research Center

  47 shared

• Antoine Royant

  Université Grenoble Alpes

  42 shared

• Eric Gouaux

  Oregon Health & Science University

  39 shared

• Ehud M. Landau

  36 shared

Labs

• Computational Structural Biology and Molecular BiophysicsPI

  Not provided

Education

• Ph.D., Bioengineering

  University of Illinois Urbana-Champaign

  2000

• M.S., Bioengineering

  University of California, San Diego

  1995

• B.S., Bioengineering

  University of California, San Diego

  1993