A5026450463- Computational Drug Discovery Methods
- Microbial Natural Products and Biosynthesis
- Tuberculosis Research and Epidemiology
- Genomics and Phylogenetic Studies
- Genetic diversity and population structure
- Antimicrobial agents and applications
- Synthesis and biological activity
- Cancer therapeutics and mechanisms
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Synthesis and Biological Evaluation
- Chemical Synthesis and Analysis
- Photochromic and Fluorescence Chemistry
- Safe Handling of Antineoplastic Drugs
- Bioinformatics and Genomic Networks
- Phenothiazines and Benzothiazines Synthesis and Activities
- Crystallography and molecular interactions
- Virology and Viral Diseases
- Marine and coastal plant biology
- Antimicrobial Resistance in Staphylococcus
- Phytochemistry and biological activities of Ficus species
- Plant Disease Resistance and Genetics
- Heme Oxygenase-1 and Carbon Monoxide
- Machine Learning in Materials Science
- Cholinesterase and Neurodegenerative Diseases
BASF (Germany)
2018-2025
Robert Bosch (Germany)
2022
University of Würzburg
2010-2021
BioMed X Institute
2016-2019
Kinome-wide screening would have the advantage of providing structure-activity relationships against hundreds targets simultaneously. Here, we report generation ligand-based activity prediction models for over 280 kinases by employing Machine Learning methods on an extensive data set proprietary bioactivity combined with open data. High quality (AUC > 0.7) was achieved ∼200 (1) combining data, (2) choosing Random Forest alternative tested methods, and (3) balancing training sets. Tests...
Photochromic cholinesterase inhibitors were obtained from cis-1,2-α-dithienylethene-based compounds by incorporating one or two aminopolymethylene tacrine groups. All target are potent acetyl- (AChE) and butyrylcholinesterase (BChE) in the nanomolar concentration range. Compound 11b bearing an octylene linker exhibited interactions with both catalytic active site (CAS) peripheral anionic (PAS) of AChE. Yet upon irradiation light, mechanism interaction varied photochromic form to another,...
Background Chloroplast-encoded genes (matK and rbcL) have been formally proposed for use in DNA barcoding efforts targeting embryophytes. Extending such a protocol to chlorophytan green algae, though, is fraught with problems including non homology (matK) heterogeneity that prevents the creation of universal PCR toolkit (rbcL). Some advocated nuclear-encoded, internal transcribed spacer two (ITS2) as an alternative traditional chloroplast markers. However, ITS2 broadly perceived be...
The internal transcribed spacer 2 (ITS2) has been used as a phylogenetic marker for more than two decades. As ITS2 research mainly focused on the very variable sequence, it confined this to low-level phylogenetics only. However, combination of sequence and its highly conserved secondary structure improves resolution(1) allows inference at multiple taxonomic ranks, including species delimitation(2-8). Database(9) presents an exhaustive dataset sequences from NCBI GenBank(11) accurately...
Nonbonding molecular interactions, such as hydrogen bonding, hydrophobic contacts, ionic etc., are at the heart of many biological processes, and their appropriate treatment is essential for successful application numerous computational drug design methods. This paper introduces GRADE, a novel interaction fingerprint (IFP) descriptor that quantifies these interactions using floating point values derived from GRAIL scores, encoding both presence quality interactions. GRADE available in two...
Abstract Motivation: With >8 million new cases in 2010, particularly documented developing countries, tuberculosis (TB) is still a highly present pandemic and often terminal. This also due to the emergence of antibiotic-resistant strains (MDR-TB XDR-TB) primary causative TB agent Mycobacterium (MTB). Efforts develop effective drugs against MTB are restrained by unique largely impermeable composition mycobacterial cell wall. Results: Based on database antimycobacterial substances (CDD...
Abstract Extensive kinase profiling data, covering more than half of the human kinome, are available nowadays and allow construction activity prediction models high practical utility. Proteochemometric (PCM) approaches use compound protein descriptors, which enables extrapolation bioactivity values to thus far unexplored kinases. In this study, potential PCM make large‐scale predictions on entire kinome is explored, considering applicability novel compounds kinases, including clinically...
One third of all drugs in clinical use owe their pharmacological activity to the functional inhibition enzymes, highlighting importance enzymatic targets for drug development. Because close relationship between and catalysis, understanding recognition turnover substrates is essential rational design. Although Staphylococcus aureus enoyl-acyl carrier protein reductase (saFabI) involved bacterial fatty acid biosynthesis constitutes a very promising target development novel, urgently needed...
Hypnales comprise over 50% of all pleurocarpous mosses. They provide a young radiation complicating phylogenetic analyses. To resolve the hypnalean phylogeny, it is necessary to use marker providing highly variable features species on one hand and conserved enabling backbone analysis other. Therefore we used internal transcribed spacer 2 (ITS2) sequences secondary structures, as deposited with ITS2 Database, simultaneously.We built an accurate in parts robustly resolved large scale phylogeny...
Matched molecular pair (MMP) analyses are widely used in compound optimization projects to gain insights into structure–activity relationships (SAR). The analysis is traditionally done via statistical methods but can also be employed together with machine learning (ML) approaches extrapolate novel compounds. here introduced MMP/ML method combines a fragment-based MMP implementation different obtain automated SAR decomposition and prediction. To test the prediction capabilities model...
An important kinetic parameter for drug efficacy is the residence time of a compound at target, which related to dissociation rate constant koff. For essential antimycobacterial target InhA, this most likely governed by ordering flexible substrate binding loop (SBL). Whereas diphenyl ether inhibitors 6PP and triclosan (TCL) do not show thus, no slow-binding inhibition high koff values, slightly modified PT70 leads an ordered 24 minutes. To assess structural differences complexes from dynamic...
Phylogenetic tree reconstruction is traditionally based on multiple sequence alignments (MSAs) and heavily depends the validity of this information bottleneck. With increasing divergence, quality MSAs decays quickly. Alignment-free methods, other hand, are abstract string comparisons avoid potential alignment problems. However, in general they not biologically motivated ignore our knowledge about evolution sequences. Thus, it still a major open question how to define an evolutionary distance...
Kinase structures in the inactive "DFG-out" state provide a wealth of druggable binding site variants. The conformational plasticity this can be mainly described by different conformations site-forming elements such as DFG motif, A-loop, P-loop, and αC-helix. Compared to DFG-in structures, DFG-out are largely underrepresented Protein Data Bank (PDB). Thus, structure-based drug design efforts for inhibitors may benefit from an efficient approach generate ensemble structures. Accordingly,...
With over 8 million new cases in 2010, particularly documented developing countries, tuberculosis (TB) is still a highly present pandemic and often terminal [1]. This also due to the emergence of antibiotic-resistant strains (MDR-TB XDR-TB) primary causative agent Mycobacterium (MTB). Efforts develop effective drugs against MTB are restrained by unique largely impermeable mycobacterial cell wall [2]. Accordingly, tools for estimating ability chemical compounds pass this barrier would...
The enoyl-acyl carrier protein (ACP) reductase (ENR) is a key enzyme within the bacterial fatty-acid synthesis pathway. It has been demonstrated that small-molecule inhibitors carrying diphenylether (DPE) scaffold bear great potential for development of highly specific and effective drugs against this class. Interestingly, different substitution patterns DPE have shown to lead varying effects on kinetic thermodynamic behavior toward ENRs from organisms. Here, we investigated effect...
Abstract Controlling phytopathogenic diseases caused by oomycete fungi is still a challenge in crop protection research. Studies on identifying new starting points to control phytopathogens revealed that the quinazolinone alkaloids febrifugine ( 1 ) and halofuginone 2 are efficiently inhibiting growth of Phytophthora infestans microtiter tests. However, despite very good vitro activity 0.13 0.06 ppm IC 50 , respectively, both compounds did not exhibit P. tomato plants. Creating homology...
The internal transcribed spacer 2 (ITS2) has been used as a phylogenetic marker for more than two decades. As ITS2 research mainly focused on the very variable sequence, it confined this to low-level phylogenetics only. However, combination of sequence and its highly conserved secondary structure improves resolution1 allows inference at multiple taxonomic ranks, including species delimitation2-8. Database9 presents an exhaustive dataset sequences from NCBI GenBank11 accurately reannotated10....