A5054651579- Enzyme Structure and Function
- Protein Structure and Dynamics
- Drug Transport and Resistance Mechanisms
- Amino Acid Enzymes and Metabolism
- Light effects on plants
- Protein purification and stability
- ATP Synthase and ATPases Research
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Mass Spectrometry Techniques and Applications
- Scientific Computing and Data Management
- Lipid Membrane Structure and Behavior
- Enzyme Catalysis and Immobilization
- Biochemical Acid Research Studies
- Photosynthetic Processes and Mechanisms
- Photoreceptor and optogenetics research
- Biochemical and Molecular Research
- Antibiotic Resistance in Bacteria
- HIV/AIDS drug development and treatment
- Microfluidic and Capillary Electrophoresis Applications
- Protein Interaction Studies and Fluorescence Analysis
- Glycosylation and Glycoproteins Research
- Machine Learning in Materials Science
- Photochemistry and Electron Transfer Studies
- Trace Elements in Health
Kettering University
2021
Rudjer Boskovic Institute
2008-2019
Memorial Sloan Kettering Cancer Center
2019
Open Geospatial Consortium
2019
Australian National University
2016-2018
The University of Queensland
2015-2018
Friedrich-Alexander-Universität Erlangen-Nürnberg
2012
Significance At this time, multidrug-resistant gram-negative bacteria are estimated to cause approximately 700,000 deaths per year globally, with a prediction that figure could reach 10 million by 2050. Antivirulence therapy, in which virulence mechanisms of pathogen chemically inactivated, represents promising approach the development treatment options. The family lipid A phosphoethanolamine transferases confers bacterial resistance innate immune defensins and colistin antibiotics....
Given the need for modern researchers to produce open, reproducible scientific output, lack of standards and best practices sharing data workflows used analyze molecular dynamics (MD) simulations has become an important issue in field. There are now multiple well-established packages perform simulations, often highly tuned exploiting specific classes hardware, each with strong communities surrounding them, but very limited interoperability/transferability options. Thus, choice software...
Despite decades of research, the mechanism action ABC multidrug transporter P-glycoprotein (P-gp) remains elusive. Due to experimental limitations, many researchers have turned molecular dynamics simulation studies in order investigate different aspects P-gp function. However, such are challenging and caution is required when interpreting results. highly flexible time scale on which it can be simulated limited. There also uncertainty regarding accuracy various crystal structures available,...
Bilirubin is a potent antioxidant that produced from the reduction of heme degradation product biliverdin. In mammalian cells and Cyanobacteria, NADH/NADPH-dependent biliverdin reductases (BVRs) Rossmann-fold have been shown to catalyze this reaction. Here, we describe characterization Rv2074 Mycobacterium tuberculosis, which belongs structurally mechanistically distinct family F420 H2 -dependent BVRs (F-BVRs) are exclusively found in Actinobacteria. We solved crystal structure bound its...
The multidrug transporter P-glycoprotein (P-gp) is central to the development of resistance in cancer. While residues essential for transport and binding have been identified, location, composition, specificity potential drug sites are uncertain. Here molecular dynamics simulations used calculate free energy profile morphine nicardipine P-gp. We show that primarily interact with key implicated from mutational studies, at different but overlapping within transmembrane pore. Their permeation...
The active sites of the (6-4) photolyases contain two conserved histidine residues, which, in Drosophila melanogaster enzyme, correspond to His365 and His369. While there are nine combinations which three possible protonation states histidines (with protons on Nδ (HID), Nε (HIE), or both (HIP)) can be paired, is presently no consensus as these present, let alone mechanistically relevant. EPR hyperfine couplings for selected FADH(•) radical have previously been used address this issue. Our...
A family of flavin/deazaflavin-dependent oxidoreductases (FDORs) from mycobacteria has been recently characterized and found to play a variety catalytic roles, including the activation prodrugs such as candidate anti-tuberculosis drug pretomanid (PA-824). However, our understanding mechanism used by these enzymes is relatively limited. To address this, we have combination quantum mechanics molecular dynamics calculations study deazaflavin-dependent nitroreductase (Ddn) Mycobacterium...
We have investigated the conformational phase spaces of both Met-enkephalin and Ada-enkephalin in 2,2,2-trifluoroethanol order to connect them their respective CD spectra. To this end, we characterized preferences zwitterionic neutral forms R- S-epimers Ada-enkephalin, as obtained by classical molecular dynamics. The spectrum for each peptide was subsequently with a procedure successive averaging, which accounts behavior solvent, side chains, backbone variations peptides. make an appropriate...
High level ab initio and density functional calculations have been employed to determine the most appropriate manner in which truncate an arginine-bound carboxylate motif, using substrate mechanism of Pyruvate Formate-Lyase as a case study. The results show that, both qualitatively quantitatively, neutral carboxylic acid provides more realistic approximation salt bridge arrangement than does bare anionic substituent.
Abstract We present an ONIOM(G3:MM) method as example of a technique capable producing chemical accuracy in the quantum mechanical (QM) treatment with molecular description context. By applying to small model systems, which we are also able calculate pure QM G3‐type results, it is possible establish reliability applies evaluating reaction mechanisms. choosing systems that relevant substrate mechanism pyruvate formate‐lyase, discuss inhibitory effect oxamate and relevance alternative...
Pyruvate formate-lyase (PFL) is a glycyl radical enzyme that converts pyruvate and coenzyme A (CoA) into formate acetyl-CoA in two half-reactions. Recently, we showed the acetylation of PFL active site first half-reaction induces subtle conformational changes, leading to opening potential channel for CoA entry. Entry crucial second half-reaction, involving acetyl transfer CoA, completion catalytic cycle. Using steered molecular dynamics (SMD) simulations, performed on acetylated...
Abstract Pyruvate formate‐lyase (PFL) catalyzes the reversible conversion of pyruvate and coenzyme A (CoA) into formate acetyl‐CoA in two half‐reactions. For second half‐reaction to take place, S−H group CoA must enter active site enzyme retrieve a protein‐bound acetyl group. However, is bound at protein surface, whereas buried interior, some 20–30 Å away. The PFL system was therefore subjected series extensive molecular dynamics simulations (in μs range) host advanced analysis procedures....
Given the need for modern researchers to produce open, reproducible scientific output, lack of standards and best practices sharing data workflows used analyze molecular dynamics (MD) simulations have become an important issue in field. There are now multiple well-established packages perform simulations, often highly tuned exploiting specific classes hardware, each with strong communities surrounding them, but very limited interoperability/transferability options. Thus, choice software...