Frank Kozielski
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View article: Structural basis for small molecule binding to the SARS-CoV-2 nsp10–nsp14 ExoN complex
Structural basis for small molecule binding to the SARS-CoV-2 nsp10–nsp14 ExoN complex Open
Coronavirus outbreaks have occurred over the past 25 years with SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) causing a global pandemic. The SARS-CoV-2 non-structural proteins 10 (nsp10) and 14 (nsp14) are considered as pote…
View article: Tetrazole-containing naphthalene bis-sulfonamide Keap1-Nrf2 interaction inhibitors with unexpected binding modes
Tetrazole-containing naphthalene bis-sulfonamide Keap1-Nrf2 interaction inhibitors with unexpected binding modes Open
Naphthalene bis-sulfonamides are amongst the most studied inhibitors of the interaction between Kelch-like ECH-associated protein-1 (Keap1), a ubiquitination facilitator protein and the nuclear factor erythroid 2-related factor 2 (Nrf2), a…
View article: Fragment-based drug discovery: A graphical review
Fragment-based drug discovery: A graphical review Open
Three decades after its introduction, fragment-based drug (or lead) discovery (FBDD or FBLD) has become a mature and powerful strategy for generating novel leads, offering distinct advantages for challenging or previously “undruggable” tar…
View article: High-confidence placement of low-occupancy fragments into electron density using the anomalous signal of sulfur and halogen atoms
High-confidence placement of low-occupancy fragments into electron density using the anomalous signal of sulfur and halogen atoms Open
Fragment-based drug design using X-ray crystallography is a powerful technique to enable the development of new lead compounds, or probe molecules, against biological targets. This study addresses the need to determine fragment binding ori…
View article: New insights into complex formation by SARS-CoV-2 nsp10 and nsp14
New insights into complex formation by SARS-CoV-2 nsp10 and nsp14 Open
SARS-CoV-2 non-structural protein 10 (nsp10) is essential for the stimulation of enzymatic activities of nsp14 and nsp16, acting as both an activator and scaffolding protein. Nsp14 is a bifunctional enzyme with the N-terminus containing a …
View article: Author Response: Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16
Author Response: Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16 Open
Full text Figures and data Side by side Abstract eLife assessment Introduction Results Discussion Materials and methods Data availability References Peer review Author response Article and author information Metrics Abstract The coronaviru…
View article: Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16
Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16 Open
The coronavirus SARS-CoV-2 protects its RNA from being recognized by host immune responses by methylation of its 5’ end, also known as capping. This process is carried out by two enzymes, non-structural protein 16 (NSP16) containing 2’-O-m…
View article: Joint Public Review: Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16
Joint Public Review: Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16 Open
The coronavirus SARS-CoV-2 protects its RNA from being recognized by host immune responses by methylation of its 5' end, also known as capping. This process is carried out by two enzymes, non-structural protein 16 (NSP16) containing 2'-O-m…
View article: Author Response: Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16
Author Response: Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16 Open
The coronavirus SARS-CoV-2 protects its RNA from being recognized by host immune responses by methylation of its 5’ end, also known as capping. This process is carried out by two enzymes, non-structural protein 16 (NSP16) containing 2’-O-m…
View article: Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16
Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16 Open
The coronavirus SARS-CoV-2 protects its RNA from being recognized by host immune responses by methylation of its 5’ end, also known as capping. This process is carried out by two enzymes, non-structural protein 16 (NSP16) containing 2’-O-m…
View article: Crystal structures and molecular dynamics simulations of a humanised antibody fragment at acidic to basic pH
Crystal structures and molecular dynamics simulations of a humanised antibody fragment at acidic to basic pH Open
View article: Oligomeric State of β-Coronavirus Non-Structural Protein 10 Stimulators Studied by Small Angle X-ray Scattering
Oligomeric State of β-Coronavirus Non-Structural Protein 10 Stimulators Studied by Small Angle X-ray Scattering Open
The β-coronavirus family, encompassing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Severe Acute Respiratory Syndrome Coronavirus (SARS), and Middle East Respiratory Syndrome Coronavirus (MERS), has triggered pandemics wit…
View article: High-Confidence Placement of Fragments into Electron Density Using Anomalous Diffraction—A Case Study Using Hits Targeting SARS-CoV-2 Non-Structural Protein 1
High-Confidence Placement of Fragments into Electron Density Using Anomalous Diffraction—A Case Study Using Hits Targeting SARS-CoV-2 Non-Structural Protein 1 Open
The identification of multiple simultaneous orientations of small molecule inhibitors binding to a protein target is a common challenge. It has recently been reported that the conformational heterogeneity of ligands is widely underreported…
View article: Oligomeric state of β-coronavirus non-structural protein 10 stimulators studied by OmniSEC and Small Angle X-ray Scattering
Oligomeric state of β-coronavirus non-structural protein 10 stimulators studied by OmniSEC and Small Angle X-ray Scattering Open
Members of the β-coronavirus family such as SARS-CoV-2, SARS, and MERS have caused pandemics over the last 20 years. Future pandemics are likely and studying the coronavirus family members is necessary for their understanding and treatment…
View article: Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16
Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16 Open
The coronavirus SARS-CoV-2 protects its RNA from being recognized by host immune responses by methylation of its 5’ end, also known as capping. This process is carried out by two enzymes, non-structural protein 16 (NSP16) containing 2’-O-m…
View article: Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16
Emerging variants of SARS-CoV-2 NSP10 highlight strong functional conservation of its binding to two non-structural proteins, NSP14 and NSP16 Open
The coronavirus SARS-CoV-2 protects its RNA from being recognized by host immune responses by methylation of its 5’ end, also known as capping. This process is carried out by two enzymes, non-structural protein 16 (NSP16) containing 2’-O-m…
View article: High-confidence placement of difficult-to-fit fragments into electron density by using anomalous signals - a case study using hits targeting SARS-CoV-2 non-structural protein 1
High-confidence placement of difficult-to-fit fragments into electron density by using anomalous signals - a case study using hits targeting SARS-CoV-2 non-structural protein 1 Open
The identification of multiple simultaneous orientations of small molecule inhibitors binding to a protein target is a common challenge. It has recently been reported that the conformational heterogeneity of ligands is widely underreported…
View article: pH-dependent crystal structures of a humanised therapeutic antibody Fab fragment: impact on molecular dynamics simulations and comparison to solution structures
pH-dependent crystal structures of a humanised therapeutic antibody Fab fragment: impact on molecular dynamics simulations and comparison to solution structures Open
Antibody-fragment (Fab) therapy development has the potential to be accelerated by computational modelling and simulations that predict their target binding, stability, formulation, manufacturability, and the impact of further protein engi…
View article: Supporting Video 01 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes
Supporting Video 01 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes Open
Time lapse imaging of untreated U2OS cells followed for 16h. Cells divide normally.
View article: Suporting Video Legends from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes
Suporting Video Legends from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes Open
SV1-SV6: Time lapse imaging of untreated, Arry-520 and ispinesib treated naive U2OS cells, Eg5(D130) and Eg5(L214) expressing U2OS cells followed for 16h. SV7-SV12: Molecular dynamics simulations of either Eg5(WT), or Eg5(D130) or Eg5(L214…
View article: Supporting Video 11 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes
Supporting Video 11 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes Open
Molecular dynamics simulations of the Eg5(D130A)-Arry-520 complex.
View article: Supporting Video 10 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes
Supporting Video 10 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes Open
Molecular dynamics simulations of the Eg5(L214A)-ispinesib complex.
View article: Supporting Video 09 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes
Supporting Video 09 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes Open
Molecular dynamics simulations of the Eg5(L214A)-Arry-520 complex.
View article: Supporting Video 08 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes
Supporting Video 08 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes Open
Molecular dynamics simulations of the wild type Eg5-ispinesib complex.
View article: Supporting Video 08 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes
Supporting Video 08 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes Open
Molecular dynamics simulations of the wild type Eg5-ispinesib complex.
View article: Supplementary Table 1 and Supplementary Figures 1-3 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes
Supplementary Table 1 and Supplementary Figures 1-3 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes Open
Table S1: Crystallographic table of data corresponding to the Eg5-Arry-520 complexes. Figure S1: Interactions of the inhibitor and conformational changes upon inhibitor binding. Figure S2: Surface representation of the allosteric inhibitor…
View article: Supporting Video 07 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes
Supporting Video 07 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes Open
Molecular dynamics simulations of the wild type Eg5-Arry-520 complex.
View article: Supporting Video 07 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes
Supporting Video 07 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes Open
Molecular dynamics simulations of the wild type Eg5-Arry-520 complex.
View article: Supporting Video 06 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes
Supporting Video 06 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes Open
Time lapse imaging of U2OS-Eg5(L214A) expressing cells exposed to 10 nM ispinesib and followed for 16h. Cells are arrested in mitosis.
View article: Supporting Video 10 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes
Supporting Video 10 from Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes Open
Molecular dynamics simulations of the Eg5(L214A)-ispinesib complex.