About

Qiang Cui is a professor in the Department of Chemistry at Boston University. His research focuses on understanding complex (bio)molecular systems through the development and application of state-of-the-art computational tools. His work aims to explore the mechanisms of biological macromolecules, enzymes, and bio-material interfaces by developing novel theoretical and computational techniques. These include improving the efficiency and accuracy of combined quantum mechanical and classical mechanical methods to study bond-breaking and bond-formation processes in realistic chemical and biological environments, as well as creating coarse-grained models for proteins and membranes to gain insights into conformational transitions, protein assembly, and membrane remodeling. Cui's group also investigates the simulation of molecular machines involved in bio-energy transduction, such as biomolecular motors and proton pumps, by analyzing their detailed mechanisms at an atomic level. His research addresses questions related to the motions, chemical coupling, and energy transduction efficiency of these complexes. Additionally, his work interfaces biology with material science, focusing on the interaction between biomolecules and inorganic materials to guide the design of hybrid materials, sensors, and sustainable nanotechnologies. Cui's background includes a B.S. in Chemical Physics from the University of Science & Technology of China, a Ph.D. in Physical Chemistry from Emory University, and postdoctoral experience at Harvard University. He has held faculty positions at the University of Wisconsin, Madison, before joining Boston University in 2018.

Research topics

• Chemistry
• Biology
• Biochemistry
• Organic chemistry
• Genetics
• Computer Science
• Biophysics
• Stereochemistry
• Cell biology
• Materials science
• Nanotechnology
• Computational biology
• Engineering
• Chemical engineering
• Crystallography
• Neuroscience
• Physics
• Evolutionary biology
• Data science
• Management science
• Photochemistry
• Optoelectronics
• Computational chemistry
• Biochemical engineering

Selected publications

• The coiled-coil domain of Escherichia coli FtsLB is a structurally detuned element critical for modulating its activation in bacterial cell division

  Journal of Biological Chemistry · 2021 · 13 citations

  • Biophysics
  • Chemistry
  • Crystallography

  The FtsLB complex is a key regulator of bacterial cell division, existing in either an off state or an on state, which supports the activation of septal peptidoglycan synthesis. In Escherichia coli, residues known to be critical for this activation are located in a region near the C-terminal end of the periplasmic coiled-coil domain of FtsLB, raising questions about the precise role of this conserved domain in the activation mechanism. Here, we investigate an unusual cluster of polar amino acids found within the core of the FtsLB coiled coil. We hypothesized that these amino acids likely reduce the structural stability of the domain and thus may be important for governing conformational changes. We found that mutating these positions to hydrophobic residues increased the thermal stability of FtsLB but caused cell division defects, suggesting that the coiled-coil domain is a "detuned" structural element. In addition, we identified suppressor mutations within the polar cluster, indicating that the precise identity of the polar amino acids is important for fine-tuning the structural balance between the off and on states. We propose a revised structural model of the tetrameric FtsLB (named the "Y-model") in which the periplasmic domain splits into a pair of coiled-coil branches. In this configuration, the hydrophilic terminal moieties of the polar amino acids remain more favorably exposed to water than in the original four-helix bundle model ("I-model"). We propose that a shift in this architecture, dependent on its marginal stability, is involved in activating the FtsLB complex and triggering septal cell wall reconstruction.

  PublisherOA PDFDOI

• Multiple deprotonation paths of the nucleophile 3′-OH in the DNA synthesis reaction

  Proceedings of the National Academy of Sciences · 2021 · 32 citations

  • Chemistry
  • Stereochemistry
  • Biochemistry

  initiates the reaction by breaking the α-β phosphodiester bond of an incoming deoxyribonucleoside triphosphate (dNTP).

  DOI

• DNMT1 reads heterochromatic H4K20me3 to reinforce LINE-1 DNA methylation

  Nature Communications · 2021 · 119 citations

  • Biology
  • Genetics
  • Cell biology

  -H4K20me3 ensures heterochromatin targeting of DNMT1 and DNA methylation at LINE-1 retrotransposons, and cooperates with the previously reported readout of histone H3 tail modifications (i.e., H3K9me3 and H3 ubiquitylation) by the RFTS domain to allosterically regulate DNMT1's activity. Interplay between RFTS and BAH1 domains of DNMT1 profoundly impacts DNA methylation at both global and focal levels and genomic resistance to radiation-induced damage. Together, our study establishes a direct link between H4K20me3 and DNA methylation, providing a mechanism in which multivalent recognition of repressive histone modifications by DNMT1 ensures appropriate DNA methylation patterning and genomic stability.

  DOI

• Biomolecular QM/MM Simulations: What Are Some of the “Burning Issues”?

  The Journal of Physical Chemistry B · 2021 · 149 citations

  1st authorCorresponding
  • Computer Science
  • Computer Science
  • Data science

  QM/MM simulations have become an indispensable tool in many chemical and biochemical investigations. Considering the tremendous degree of success, including recognition by a 2013 Nobel Prize in Chemistry, are there still "burning challenges" in QM/MM methods, especially for biomolecular systems? In this short Perspective, we discuss several issues that we believe greatly impact the robustness and quantitative applicability of QM/MM simulations to many, if not all, biomolecules. We highlight these issues with observations and relevant advances from recent studies in our group and others in the field. Despite such limited scope, we hope the discussions are of general interest and will stimulate additional developments that help push the field forward in meaningful directions.

  DOI

• Artificial Intracellular Filaments

  Cell Reports Physical Science · 2020 · 73 citations

  • Biophysics
  • Chemistry
  • Biochemistry

  formation of self-limiting intracellular filaments of a small peptide via enzymatic morphological transition of a phosphorylated and trimethylated heterochiral tetrapeptide. Enzymatic dephosphorylation reduces repulsive intermolecular electrostatic interactions and converts the peptidic nanoparticles into filaments, which exhibit distinct types of cross-β structures with either C7 or C2 symmetries, with the hydrophilic C-terminal residues at the periphery of the helix. Macromolecular crowding promotes the peptide filaments to form bundles, which extend from the plasma membrane to nuclear membrane and hardly interact with endogenous components, including cytoskeletons. Stereochemistry and post-translational modification (PTM) of peptides are critical for generating the intracellular bundles. This work may offer a way to gain lost functions or to provide molecular insights for understanding normal and aberrant intracellular filaments.

  DOI

• Functional plasticity and evolutionary adaptation of allosteric regulation

  Proceedings of the National Academy of Sciences · 2020 · 110 citations

  • Computational biology
  • Biology
  • Neuroscience

  Allostery is a fundamental regulatory mechanism of protein function. Despite notable advances, understanding the molecular determinants of allostery remains an elusive goal. Our current knowledge of allostery is principally shaped by a structure-centric view, which makes it difficult to understand the decentralized character of allostery. We present a function-centric approach using deep mutational scanning to elucidate the molecular basis and underlying functional landscape of allostery. We show that allosteric signaling exhibits a high degree of functional plasticity and redundancy through myriad mutational pathways. Residues critical for allosteric signaling are surprisingly poorly conserved while those required for structural integrity are highly conserved, suggesting evolutionary pressure to preserve fold over function. Our results suggest multiple solutions to the thermodynamic conditions of cooperativity, in contrast to the common view of a finely tuned allosteric residue network maintained under selection.

  DOI

• Multicolor polymeric carbon dots: synthesis, separation and polyamide-supported molecular fluorescence

  Chemical Science · 2020 · 125 citations

  • Materials science
  • Nanotechnology
  • Chemistry

  Multicolor carbon dots (CDs) have been developed recently and demonstrate great potential in bio-imaging, sensing, and LEDs. However, the fluorescence mechanism of their tunable colors is still under debate, and efficient separation methods are still challenging. Herein, we synthesized multicolor polymeric CDs through solvothermal treatment of citric acid and urea in formamide. Automated reversed-phase column separation was used to achieve fractions with distinct colors, including blue, cyan, green, yellow, orange and red. This work explores the physicochemical properties and fluorescence origins of the red, green, and blue fractions in depth with combined experimental and computational methods. Three dominant fluorescence mechanism hypotheses were evaluated by comparing time-dependent density functional theory and molecular dynamics calculation results to measured characteristics. We find that blue fluorescence likely comes from embedded small molecules trapped in carbonaceous cages, while pyrene analogs are the most likely origin for emission at other wavelengths, especially in the red. Also important, upon interaction with live cells, different CD color fractions are trafficked to different sub-cellular locations. Super-resolution imaging shows that the blue CDs were found in a variety of organelles, such as mitochondria and lysosomes, while the red CDs were primarily localized in lysosomes. These findings significantly advance our understanding of the photoluminescence mechanism of multicolor CDs and help to guide future design and applications of these promising nanomaterials.

  DOI

• Single-Step Replacement of an Unreactive C–H Bond by a C–S Bond Using Polysulfide as the Direct Sulfur Source in the Anaerobic Ergothioneine Biosynthesis

  ACS Catalysis · 2020 · 28 citations

  • Chemistry
  • Stereochemistry
  • Organic chemistry

  C-H bond in this trans-sulfuration reaction.

  DOI

• Direct readout of heterochromatic H3K9me3 regulates DNMT1-mediated maintenance DNA methylation

  Proceedings of the National Academy of Sciences · 2020 · 114 citations

  • Biology
  • Cell biology
  • Genetics

  In mammals, repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3), frequently coexist with DNA methylation, producing a more stable and silenced chromatin state. However, it remains elusive how these epigenetic modifications crosstalk. Here, through structural and biochemical characterizations, we identified the replication foci targeting sequence (RFTS) domain of maintenance DNA methyltransferase DNMT1, a module known to bind the ubiquitylated H3 (H3Ub), as a specific reader for H3K9me3/H3Ub, with the recognition mode distinct from the typical trimethyl-lysine reader. Disruption of the interaction between RFTS and the H3K9me3Ub affects the localization of DNMT1 in stem cells and profoundly impairs the global DNA methylation and genomic stability. Together, this study reveals a previously unappreciated pathway through which H3K9me3 directly reinforces DNMT1-mediated maintenance DNA methylation.

  DOI

Recent grants

• NIH Grant R01GM07142802

  NIH · $202k · 2010

• New methods for treating electrostatics and adaptive partitioning in QM/MM simulations

  NSF · $410k · 2010–2013

• Multi-scale simulation methods for energy transduction and macromolecular assembly

  NSF · $424k · 2018–2021

• Development of multi-scale models for enzyme catalysis in complex environments

  NSF · $405k · 2013–2017

• Multi-scale simulation methods for energy transduction and macromolecular assembly

  NSF · $450k · 2017–2018

Frequent coauthors

• Keiji Morokuma

  Kyoto University

  173 shared

• Marcus Elstner

  Karlsruhe Institute of Technology

  120 shared

• Martin Karplus

  Harvard University

  61 shared

• Haibo Yu

  University of Wollongong

  54 shared

• Djamaladdin G. Musaev

  Atlanta University Center

  44 shared

• Hua Guo

  University of Oxford

  42 shared

• Dingguo Xu

  Sichuan University

  41 shared

• Demian Riccardi

  Material Measurement Laboratory

  40 shared

Education

• Postdoctoral fellow, Chemistry and Chemical Biology

  Harvard University

  2001

• Ph. D., Chemistry

  Emory University

  1997

• B. S. , Chemical Physics

  University of Science and Technology of China

  1993

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