A5018926605- Protein Structure and Dynamics
- Enzyme Structure and Function
- Computational Drug Discovery Methods
- Scientific Computing and Data Management
- Distributed and Parallel Computing Systems
- RNA and protein synthesis mechanisms
- Machine Learning in Materials Science
- Bioinformatics and Genomic Networks
- Microbial Natural Products and Biosynthesis
- Advanced Data Storage Technologies
- Erythrocyte Function and Pathophysiology
- Advanced Electron Microscopy Techniques and Applications
- Calcium signaling and nucleotide metabolism
- Receptor Mechanisms and Signaling
- Digital and Cyber Forensics
- Model-Driven Software Engineering Techniques
- Data-Driven Disease Surveillance
- Forensic and Genetic Research
- RNA Research and Splicing
- Malaria Research and Control
- Trypanosoma species research and implications
- Neuropeptides and Animal Physiology
- Ethics in Clinical Research
- Genomics and Chromatin Dynamics
- Anomaly Detection Techniques and Applications
Utrecht University
2016-2024
University Medical Center Utrecht
2024
Boğaziçi University
2008-2017
Zero to Three
2011
We present the performance of HADDOCK, our information-driven docking software, in second edition D3R Grand Challenge. In this blind experiment, participants were requested to predict structures and binding affinities complexes between Farnesoid X nuclear receptor 102 different ligands. The models obtained Stage1 with HADDOCK ligand-specific protocol show an average ligand RMSD 5.1 Å from crystal structure. Only 6/35 targets within 2.5 reference, which prompted us investigate limiting...
This paper describes the achievements of H2020 project INDIGO-DataCloud. The has provided e-infrastructures with tools, applications and cloud framework enhancements to manage demanding requirements scientific communities, either locally or through enhanced interfaces. middleware developed allows federate hybrid resources, easily write, port run cloud. In particular, we have extended existing PaaS (Platform as a Service) solutions, allowing public private e-infrastructures, including those...
Structure determination of complex molecular machines requires a combination an increasing number experimental methods with highly specialized software geared toward each data source to properly handle the gathered data. Recently, we introduced two packages PowerFit and DisVis. These combine high-resolution structures atomic subunits density maps from cryo-electron microscopy or distance restraints, typically acquired by chemical cross-linking coupled mass spectrometry, respectively. Here,...
Accurate sampling of conformational space and, in particular, the transitions between functional substates has been a challenge molecular dynamic (MD) simulations large biomolecular systems. We developed an Elastic Network Model (ENM)-based computational method, ClustENM, for changes biomolecules with various sizes and oligomerization states. ClustENM is iterative method that combines ENM energy minimization clustering steps. It unbiased technique, which requires only initial structure as...
ABSTRACT Our information‐driven docking approach HADDOCK is a consistent top predictor and scorer since the start of its participation in CAPRI community‐wide experiment. This sustained performance due, part, to ability integrate experimental data and/or bioinformatics information into modelling process, also overall robustness scoring function used assess rank predictions. In CASP‐CAPRI Round 1 experiment we successfully selected acceptable/medium quality models for 18/14 25 targets –...
Catalytic loop motions facilitate substrate recognition and binding in many enzymes. While these appear to be highly flexible, their functional significance suggests that structure-encoded preferences may play a role selecting particular mechanisms of motions. We performed an extensive study on set enzymes assess whether the collective/global dynamics, as predicted by elastic network models (ENMs), facilitates or even defines local undergone loops. Our dataset includes total 117 crystal...
Incorporating the dynamic nature of biomolecules in modeling their complexes is a challenge, especially when extent and direction conformational changes taking place upon binding unknown. Estimating whether biomolecule to its partner(s) occurs state accessible unbound form ("conformational selection") and/or process induces ("induced-fit") another challenge. We propose here method combining sampling using ClustENM-an elastic network-based procedure-with docking HADDOCK, framework that...
The collective dynamics of the nascent polypeptide exit tunnel are investigated with computationally efficient elastic network model using normal mode analysis. calculated modes considered individually and in linear combinations different coefficients mimicking phase angles between modes, order to follow mechanistic motions wall residues. low frequency fluctuations indicate three distinct regions along tunnel-the entrance, neck, exit-each having distinctly domain motions. Generally, lining...
Incorporating receptor flexibility in small ligand-protein docking still poses a challenge for proteins undergoing large conformational changes. In the absence of bound structures, sampling conformers that are accessible by apo state may facilitate and drug design studies. For this aim, we developed an unbiased search algorithm, integrating global modes from elastic network model, clustering energy minimization with implicit solvation. Our dataset consists five diverse to complex RMSDs...
Abstract Our information‐driven docking approach HADDOCK has demonstrated a sustained performance since the start of its participation to CAPRI. This is due, in part, ability integrate data into modeling process, and robustness scoring function. We participated CAPRI both as server manual predictors. In rounds 38‐45, we have used various strategies depending on available information. These ranged from imposing restraints few residues identified literature being important for interaction,...
G-Protein coupled receptors (GPCRs) are involved in a myriad of pathways key for human physiology through the formation complexes with intracellular partners such as G-proteins and arrestins (Arrs). However, structural dynamical determinants these still largely unknown. Herein, we developed computational big-data pipeline that enables characterization GPCR no available structure. This was used to study well-known group catecholamine receptors, dopamine receptor (DXR) family its complexes,...
Abstract We aim to uncover the binding modes of benzothiazoles, which have been reported as specific inhibitors triosephosphate isomerase from parasite Trypanosoma cruzi (TcTIM), by performing blind dockings on both TcTIM and human TIM (hTIM). Detailed analysis sites interactions are carried out based ensemble multiple receptor conformers obtained molecular dynamics simulations. In dimer dockings, preferentially bind tunnel‐shaped cavity formed at interface subunits, whereas non‐inhibitors...
The chaperone trigger factor (TF) binds to the ribosome exit tunnel and helps cotranslational folding of nascent chains (NC) in bacterial cells chloroplasts. In this study, we aim investigate functional dynamics fully-atomistic apo TF its complex with 50S. As accomodates a high percentage charged residues on surface, effect ionic strength is assessed here by performing five independent molecular (MD) simulations (total 1.3 micro-second duration) at 29 mM 150 strengths. At both...
The opening/closure of the catalytic loop 6 over active site in apo triosephosphate isomerase (TIM) has been previously shown to be driven by global motions enzyme, specifically counter-clockwise rotation subunits. In this work, effect substrate dihydroxyacetone phosphate (DHAP) on TIM dynamics is assessed using two and DHAP-bound molecular (MD) trajectories (each 60 ns long). Multiple events take place during runs for both its DHAP-complex. However, observed suppressed bending-type are...
Abstract Objective Methods Several statistical analysis plans (SAP) from the Vaccine Monitoring Collaboration for Europe (VAC4EU) were analyzed to identify study design sections and specifications programming RWE studies based on multi-databases standardized common data models. We envisioned a metadata schema that transforms epidemiologist’s knowledge into machine-readable format. This must also contain different sections, code lists, time anchoring specified in SAPs. Further desired...
ABSTRACT Objective To enhance documentation on programming decisions in Real World Evidence (RWE) studies. Materials and Methods We analyzed several statistical analysis plans (SAP) within the Vaccine Monitoring Collaboration for Europe (VAC4EU) to identify study design sections specifications RWE designed a machine‐readable metadata schema containing sections, codelists, time anchoring definitions specified SAPs with adaptability user‐friendliness. Results developed RWE‐BRIDGE, form of...
Conformational dynamics and flexibility form the link between protein structure function. Molecular (MD) simulations have been valuable for our understanding of conformational energy landscape at atomic scale, which is difficult to probe experimentally. In this respect, essential proteins revealed by principal component analysis MD simulation data provide information on functional motions that generally bear a collective nature. review, we summarize literature statistical with an emphasis...
Conformational dynamics and flexibility form the link between protein structure function. Molecular (MD) simulations have been valuable for our understanding of conformational energy landscape at atomic scale, which is difficult to probe experimentally. In this respect, essential proteins revealed by principal component analysis MD simulation data provide information on functional motions that generally bear a collective nature. review, we summarize literature statistical with an emphasis...
ABSTRACT Our information-driven docking approach HADDOCK has demonstrated a sustained performance since the start of its participation to CAPRI. This is due, in part, ability integrate data into modelling process, and robustness scoring function. We participated CAPRI both as server manual predictors. In rounds 38-45, we have used various strategies depending on information at hand. These ranged from imposing restraints few residues identified literature being important for interaction,...