A5005051901- Enzyme Structure and Function
- Protein Structure and Dynamics
- Computational Drug Discovery Methods
- Melanoma and MAPK Pathways
- Mass Spectrometry Techniques and Applications
- DNA and Nucleic Acid Chemistry
- DNA Repair Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Nerve injury and regeneration
- Crystallization and Solubility Studies
- Nuclear Receptors and Signaling
- RNA and protein synthesis mechanisms
- Biochemical and Molecular Research
- Silk-based biomaterials and applications
- HER2/EGFR in Cancer Research
- Autophagy in Disease and Therapy
- Blood groups and transfusion
- Peptidase Inhibition and Analysis
- Health Sciences Research and Education
- Probabilistic and Robust Engineering Design
- Signaling Pathways in Disease
- Blood properties and coagulation
- Gene expression and cancer classification
- Health and Medical Research Impacts
- Control Systems and Identification
University College London
2018-2021
Institute of Structural and Molecular Biology
2019-2020
Institute for Research in Biomedicine
2017-2019
Universitat Politècnica de Catalunya
2018-2019
Barcelona Supercomputing Center
2019
University of Vienna
2011-2014
Max Perutz Labs
2011-2014
Vienna Biocenter
2011-2012
Goethe University Frankfurt
2012
Mediterranean Institute for Life Sciences
2010-2011
Biomolecular simulation is increasingly central to understanding and designing biological molecules their interactions. Detailed, physics‐based methods are demonstrating rapidly growing impact in areas as diverse biocatalysis, drug delivery, biomaterials, biotechnology, design. Simulations offer the potential of uniquely detailed, atomic‐level insight into mechanisms, dynamics, processes, well accurate predictions molecular properties. can now be used computational assays activity, for...
Abstract Biomolecular X-ray structures typically provide a static, time- and ensemble-averaged view of molecular ensembles in crystals. In the absence rigid-body motions lattice defects, B-factors are thought to accurately reflect structural heterogeneity such ensembles. order study effects averaging on B-factors, we employ dynamics simulations controllably manipulate microscopic crystal containing 216 copies villin headpiece. Using average structure factors derived from simulation, analyse...
Abstract Our current understanding of epidermal growth factor receptor (EGFR) autoinhibition is based on X-ray structural data monomer and dimer fragments does not explain how mutations achieve ligand-independent phosphorylation. Using a repertoire imaging technologies simulations we reveal an extracellular head-to-head interaction through which ligand-free polymer chains various lengths assemble. The architecture the prevents kinase-mediated dimerisation. latter, afforded by mutation or...
p38α is a Ser/Thr protein kinase involved in variety of cellular processes and pathological conditions, which makes it promising pharmacological target. Although the activity enzyme highly regulated, its molecular mechanism activation remains largely unexplained, even after decades research. By using state-of-the-art dynamics simulations, we decipher key elements complex refined by evolution to allow for fine tuning activity. Our study describes first time effects different regulators...
Whether recent updates and new releases of atomistic force fields can model the structural dynamical properties proteins containing both folded partially disordered domains is still unclear. To address this fundamental question, we tested eight recently released against our set nuclear magnetic resonance (NMR) observables for a complex medically relevant system, major factor VIII binding region on von Willebrand factor. This biomedically important comprises structured domain. By using an...
We study the contribution of linear, pairwise atom-positional correlations (covariances) to absolute and relative conformational entropy as calculated by quasi-harmonic analysis molecular dynamics (MD) trajectories (SQH ΔSQH). By analyzing a total 25 μs MD simulations ubiquitin six its binding partners in bound unbound states, 2.4 eight different proteins phosphorylated unphosphorylated we show that ΔSQH represents remarkably constant fraction change obtained if one ignores covariance terms...
Significance In response to stress, cells can activate several mechanisms that support functionality and survival. However, strong or persistent stresses usually trigger a deleterious answer leads cell death. The protein kinases p38α MK2 are implicated in stress-signaling pathway. Here, we characterize molecular mechanism helps translate the stress-induced activation of p38α–MK2 pathway into appropriate biological responses. We show MK2-expression levels regulated by stress intensity...
Atomic positions obtained by X-ray crystallography are time and space averages over many molecules in the crystal. Importantly, interatomic distances, calculated between such average frequently used structural mechanistic analyses, can be substantially different from more appropriate time-average ensemble-average distances. Using crystallographic B-factors, one deduce corrections, which have so far been applied exclusively to small molecules, obtain correct distances as a function of type...
Protein crystallization is frequently induced by the addition of various precipitants, which directly affect protein solubility. In to organic cosolvents and long-chain polymers, salts belong most widely used precipitants in crystallography. However, despite such widespread usage, their mode action at atomistic level still largely unknown. Here, we perform extensive molecular dynamics simulations villin headpiece crystal unit cell examine its stability different concentrations sodium...
ABSTRACT X-ray crystallography has been traditionally considered as the primary tool for determination of biomolecular structures and its derived models are taken gold standard in structural biology. However, contacts formed through crystal lattice known to affect structures, especially case small flexible molecules, like DNA oligos, introducing drastic changes structure with respect solution phase. Furthermore, it is still unknown why molecules crystallize certain symmetry groups how...
The ab initio treatment of molecular crystals in due consideration space group symmetry is still an underdeveloped field.Quantumcrysca innovative attempt to calculate the energy periodical systems by quantum-mechanical means including full using a QM-MM-approach.Dividing crystal disjunct spherical regions gives rise shell-model.All interactions between atoms inner sphere are treated on quantum mechanical level, whereas outer and calculated classical force-fields.A reliable calculation weak...
Abstract Nerve Growth Factor (NGF) is an important neurotrophic factor involved in the regulation of cell differentiation, maintenance, growth and survival target neurons. Expressed as a proNGF precursor, NGF then matured by furin-mediated protease cleavage. Increasing evidence suggests that have distinct cellular partners which account for different functional roles. While structure mature available, little known about pro-domain within context because dynamical structural features protein...