Lewandowski Group

Lewandowski group focuses on development and applications of solid-state and solution NMR to study structure, dynamics and interactions of biological systems in the context of integrated structural biology. We are associated with the Warwick solid-state NMR grouping and Chemical Biology Research Facility.

Research Themes | NMR Facilities | Available Positions

Solid-State NMR Methodology

We develop methods to probe structure and dynamics of molecules.

Protein structure & interactions

We apply both solid- and solution-state NMR to various biomolecular systems.

Natural products biosynthesis

Structural biology and engineering of natural products biosynthetic machinery.

Protein dynamics

Experimental determination and simulation of molecular motion.

Antibiotics

Understanding modes of action and facilitating designing new antibiotics.

News

Follow @lewandowskilab

May 2023: Spin diffusion at fast spinning (read in J Chem Phys (Editor's Pick))
Oct 2022: Slice & Dice longitudinal relaxation measurements (read in PCCP)
It's cover time: we got three covers on three different consecutive papers in three different journals
Aug 2021: Paper in JMR on simultaneous measurements of ¹⁵N and ¹³C' relaxation. Featured on the cover.
Jul 27 2021: Our opus on COM domains accepted in ACS Catalysis
Jun 16 2021: Koorosh Fatemian defends his PhD thesis
Feb 12 2020: JMR Award for an outstanding paper for Angelo's and Trent's manuscript on multiple receivers for protein assignment to be presented at 61st ENC
Dec 30 2019: First paper from Sarah PhD in Mol. Pharmaceutics
Sept 23 2019: Paper in Nat Chem on integrated structural biology of systems involved in chain termination of antibiotic enacyloxin biosynthesis. Press release.
Jul 31 2019: Paper in Sci Rep on accelerated relaxation dispersion in GB1:IgG complex
Jul 6th 2019: Paper in J Magn Reson on multiple receiver experiments for protein assignment

MAS rotors versus maximum spinning frequency and volume (click for a larger image)

Solid-State NMR Methodology Development

We develop solid-state NMR methods for studying structures and dynamics of proteins.

Highlights:

NMR relaxation and methodology at 60-111 kHz magic angle spinning (PCCP 2015).
Characterisation of structure and dynamics of large protein complexes (JACS 2014, Angew. Chem. 2015)
Solvent PREs for characterisation of protein-protein interfaces in large complexes (JACS 2017)
Accelerated R_1ρ relaxation dispersion for application in large complexes (SciRep 2019)

Protein structure determination and molecular interactions

We employ a combination of different structural biology and biophysical methods led by solid-state and solution-state NMR to investigate structure, dynamics and interactions of various biological systems. We work on systems that are natural targets for solid-state NMR, e.g. nanocrystalline proteins, protein complexes (e.g. protein-antibody complexes and complexes from polyketide synthases), fibrils and membrane proteins and systems that benefit from combined solution/solid state NMR approaches. We are also interested in characterization of molecular interactions, in particular protein interactions with other proteins, ligands and nucleic acids.

Main areas:

natural products biosynthesis (polyketide synthases) (Nat. Chem. Biol. 2018, Nat. Chem. 2019)
lipid II binding antibiotics, e.g. teixobactin (Chem. Sci. 2018)
peptidoglycan biosynthesis

Protein dynamics

We apply a variety of methods centered around NMR to characterize protein motions at atomic resolution.

Highlights:

dynamics of GB1 in a >300 kDa complex with full length immunoglobulin (Angew. Chem. 2015)
protein "dynamic transitions" through the lens of variable temperature relaxation measurements in a crystalline protein (Science 2015)
peptide plane fluctuations from joint ¹⁵N and ¹³C' relaxation measurements (PhysChemChemPhys 2015)

Structural biology and engineering of systems involved in natural products biosynthesis

We employ NMR-led integrated structural biology approach to study mechanistic details of various PKS/NRPS biosythetic pathways.

Highlights:

Structural basis for chain release from the enacyloxin polyketide synthase. Integrated structural biology approach (Nat. Chem. 2019)
Mechanism of intersubunit ketosynthase–dehydratase interaction in polyketide synthases (Nat. Chem. Biol. 2018)
Review on the protein-protein interactions in trans-AT PKSs (Nat. Prod. Rep. 2018)

NMR facilities

(NMR hall in Millburn House)

The group uses mostly 2 x 500 MHz (various MAS probes from 4 mm to 1.3 mm), 600 MHz (various MAS probes from 4 mm to 1.3 mm, a unique 0.8 mm 100 kHz probe from Ago Samoson; upgraded to a new Avance Neo console in 2021 funded by BBSRC ALERT19 BB/V50967X/1 ). We are also frequent users of the the UK High-Field Solid-State NMR Facility (850 MHz, 1 GHz and soon 1.2 GHz spectrometers).

(NMR hall in MAS building - left to right: solid-state NMR: 700 MHz WB spectrometer with 0.7, 1.3 and 3.2 mm MAS probes, solution NMR: 500 MHz, 600 MHz, 700 MHz with cryoprobe - upgrade to new console and TCI and TXO cryoprobes in 2023 funded by BBSRC ALERT21 BB/W020297/1).

The group is the main user of the ERC & UW funded 700 MHz solid-state NMR spectrometer and frequent users of 700 MHz and 600 MHz solution NMR spectrometers. More details on the facilities in the Department of Chemistry.

NMR Hall in MAS building