A5068377776- Protein Structure and Dynamics
- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Enzyme Structure and Function
- Enzyme Production and Characterization
- Spectroscopy and Quantum Chemical Studies
- Rice Cultivation and Yield Improvement
- Theoretical and Computational Physics
- Microbial Metabolites in Food Biotechnology
- Microbial Metabolic Engineering and Bioproduction
- Enzyme Catalysis and Immobilization
- Advanced Chemical Physics Studies
- Monoclonal and Polyclonal Antibodies Research
- Diet, Metabolism, and Disease
- Advanced Thermodynamics and Statistical Mechanics
- Machine Learning in Materials Science
- Polysaccharides and Plant Cell Walls
- RNA and protein synthesis mechanisms
- Bioinformatics and Genomic Networks
- Mass Spectrometry Techniques and Applications
- Molecular Junctions and Nanostructures
- Toxin Mechanisms and Immunotoxins
- Computational Drug Discovery Methods
- Magnetic and Electromagnetic Effects
- Genetics, Bioinformatics, and Biomedical Research
University of Chemistry and Technology, Prague
2016-2025
Slovak Academy of Sciences
2008-2013
Institute of Chemistry of the Slovak Academy of Sciences
2009-2011
Institute of Chemical Technology
2005-2008
Paul Scherrer Institute
2008
ETH Zurich
2006-2008
New Huadu Business School
2005
In computational physics, chemistry, and biology, the implementation of new techniques in shared open-source software lowers barriers to entry promotes rapid scientific progress. However, effectively training users presents several challenges. Common methods like direct knowledge transfer in-person workshops are limited reach comprehensiveness. Furthermore, while COVID-19 pandemic highlighted benefits online training, traditional tutorials can quickly become outdated may not cover all...
RNA hairpins capped by 5'-GNRA-3' or 5'-UNCG-3' tetraloops (TLs) are prominent structural motifs. Despite their small size, a wealth of experimental data, and recent progress in theoretical simulations dynamics folding, our understanding the folding unfolding processes these elements is still limited. Theoretical description requires robust sampling, which can be achieved either an exhaustive time scale standard molecular sophisticated enhanced sampling methods, using temperature...
The CACHE challenges are a series of prospective benchmarking exercises to evaluate progress in the field computational hit-finding. Here we report results inaugural challenge which 23 teams each selected up 100 commercially available compounds that they predicted would bind WDR domain Parkinson's disease target LRRK2, with no known ligand and only an apo structure PDB. lack binding data presumably low druggability is hit finding methods. Of 1955 molecules by participants Round 1 challenge,...
Atomic motions in molecules are not linear. This infers that nonlinear dimensionality reduction methods can outperform linear ones analysis of collective atomic motions. In addition, be used as potentially efficient guides for biased simulation techniques. Here we present a with bias potential acting the directions determined by method. Ad hoc generated conformations trans,trans-1,2,4-trifluorocyclooctane were analyzed Isomap method to map these 72-dimensional coordinates three dimensions,...
Galectin-3 (Gal-3) is recognized as a prognostic marker in several cancer types. Its involvement tumor development and proliferation makes this lectin promising target for early diagnosis anti-cancer therapies. Gal-3 recognizes poly-N-acetyllactosamine (LacNAc)-based carbohydrate motifs of glycoproteins glycolipids with high specificity internal LacNAc epitopes. This study analyzes the mode kinetics binding to series multivalent neo-glycoproteins presenting complex poly-LacNAc-based...
Molecular simulation trajectories represent high-dimensional data. Such data can be visualized by methods of dimensionality reduction. Non-linear reduction are likely to more efficient than linear ones due the fact that motions atoms non-linear. Here we test a popular non-linear t-distributed Stochastic Neighbor Embedding (t-SNE) method on analysis 200 ns alanine dipeptide dynamics and 208 μs Trp-cage folding unfolding. Furthermore, introduce time-lagged variant t-SNE in order focus rarely...
The potential of molecular simulations is limited by their computational costs. There often a need to accelerate using some the enhanced sampling methods. Metadynamics applies history-dependent bias that disfavors previously visited states. To apply metadynamics, it necessary select few properties system─collective variables (CVs) can be used define potential. Over past years, there have been emerging opportunities for machine learning and, in particular, artificial neural networks within...
Design of new proteins is often formulated as an optimization task. An amino acid sequence characterized by energy, and this energy sampled minimized. Here, we use a parallel tempering algorithm to accelerate A series 100- or 200-residue was designed using modified Evolutionary Scale Modeling design module maximize the confidence in structure prediction globularity minimize surface hydrophobic residues. We show that viable alternative Monte Carlo sampling simulated annealing related...
Recent studies suggest CNNM2 (cyclin M2) to be part of the long-sought basolateral Mg2+ extruder at renal distal convoluted tubule, or its regulator. In present study, we explore structural features and ligand-binding capacities Bateman module (residues 429-584), an intracellular domain structurally equivalent region involved in handling by bacterial transporter MgtE, AMP binding efflux protein CorC. Additionally, studied impact pathogenic mutation T568I located this region. Our crystal...
The state of a molecular system can be described in terms collective variables. These low-dimensional descriptors structure used to monitor the simulation, calculate free energy profiles or accelerate rare events by bias potential force. Frequent calculation some complex variables may slow down simulation analysis trajectories. Moreover, many cannot explicitly calculated for newly sampled structures. In order address this problem, we developed new package called anncolvar. This makes it...
Phenotypic screening of an in-house library small molecule purine derivatives against Mycobacterium tuberculosis (Mtb) led to the identification 2-morpholino-7-(naphthalen-2-ylmethyl)-1,7-dihydro-6H-purin-6-one 10 as a potent antimycobacterial agent with MIC99 4 μM. Thorough structure-activity relationship studies revealed importance 7-(naphthalen-2-ylmethyl) substitution for activity, yet opened possibility structural modifications at positions 2 and 6 core. As result, optimized analogues...
The free-energy surface (FES) of glycyl-phenylalanyl-alanine (GFA) tripeptide was explored by molecular dynamics (MD) simulations in combination with high-level correlated ab initio quantum chemical calculations and metadynamics. Both the MD metadynamics employed tight-binding DFT-D method instead AMBER force field, which yielded inaccurate results. We classified minima localised FESs as follows: a) backbone-conformational arrangement; b) existence a COOH...OC intramolecular H-bond (families...