A5089298082- Enzyme function and inhibition
- Computational Drug Discovery Methods
- Synthesis and Catalytic Reactions
- Protein Structure and Dynamics
- Click Chemistry and Applications
- Phenothiazines and Benzothiazines Synthesis and Activities
- Advanced Chemical Physics Studies
- Enzyme Structure and Function
- Cholinesterase and Neurodegenerative Diseases
- Chemical Reactions and Mechanisms
- HIV/AIDS drug development and treatment
- Biochemical and Molecular Research
- Spectroscopy and Quantum Chemical Studies
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Molecular Junctions and Nanostructures
- Bioactive Compounds and Antitumor Agents
- Synthesis and Reactivity of Heterocycles
- Electrochemical sensors and biosensors
- Machine Learning in Materials Science
- RNA and protein synthesis mechanisms
- Metabolomics and Mass Spectrometry Studies
- Chemical Synthesis and Analysis
- Lipid Membrane Structure and Behavior
- Synthesis and Biological Evaluation
Vilnius University
2016-2025
Czech Academy of Sciences, Institute of Biotechnology
2014-2024
Universidade da Madeira
2006-2012
Biotechnology Institute
2002-2010
Massachusetts Institute of Technology
2008
University of Massachusetts Chan Medical School
2008
Advanced Bioscience Laboratories (United States)
2004
University of Iowa
1999-2001
University of Hawaii System
1997-1999
The effective fragment potential (EFP) method is described and its capabilities illustrated using several applications. original method, EFP1, was primarily developed to describe aqueous solvation, by representing Coulombic, induction repulsive interactions via one-electron terms in the ab initio Hamiltonian. It demonstrated, water clusters, Menshutkin reaction glycine neutral/zwitterion equilibrium, that agreement with both fully calculations experiment are excellent. More recently, model...
A syntax-correcting CIF parser, COD::CIF::Parser, is presented that can parse 1.1 files and accurately report the position nature of discovered syntactic problems. In addition, parser able to automatically fix most common obvious deficiencies input files. Bindings for Perl, C Python programming environments are available. Based on cod-tools package manipulating CIFs in Crystallography Open Database (COD) has been developed. The successfully used continuous updates data automated COD...
Human carbonic anhydrase IX (CA IX) is highly expressed in tumor tissues, and its selective inhibition provides a potential target for the treatment of numerous cancers. Development potent, inhibitors against this remains an unmet need anticancer therapeutics. A series fluorinated benzenesulfonamides with substituents on benzene ring was designed synthesized. Several these exhibited potent profile CA IX. Three fluorine atoms significantly increased affinity by withdrawing electrons lowering...
A computational methodology to treat the covalent boundary between QM and MM regions in Effective Fragment Potential (EFP) method, by defining a buffer region consisting of frozen localized molecular orbitals (LMOs), is introduced. The implementation energy, gradient, EFP parameter evaluations presence LMOs discussed. magnitude source errors introduced various choices studied for proton affinities lysine tripeptide glycine-lysine-glycine. It shown that reasonable choice density affinity...
ABSTRACT Drug resistance mutations in HIV-1 protease selectively alter inhibitor binding without significantly affecting substrate recognition and cleavage. This alteration molecular led us to develop the substrate-envelope hypothesis which predicts that inhibitors fit within overlapping consensus volume of substrates are less likely be susceptible drug-resistant mutations, as a mutation impacting such would simultaneously impact processing substrates. To evaluate this hypothesis, over 130...
The acquisition of drug-resistant mutations by infectious pathogens remains a pressing health concern, and the development strategies to combat this threat is priority. Here we have applied general strategy, inverse design using substrate envelope, develop inhibitors HIV-1 protease. Structure-based computation was used predicted stay within consensus volume in binding site. Two rounds design, synthesis, experimental testing, structural analysis were carried out, resulting total 51 compounds....
In the absence of an experimentally solved structure, a homology model protein target can be used instead for virtual screening drug candidates by docking and scoring. This approach poses number questions regarding choice template to use in constructing model, accuracy results, importance allowing flexibility. The present study addresses such with compound calculations multiple models five targets. A central result is that frequently yields enrichments known ligands as good obtained crystal...
In this work we aim to show how Genome Scale Metabolic Models (GSMMs) can be used as tools for drug design. By comparing the chemical structures of human metabolites (obtained using their KEGG indexes) and compounds contained in DrugBank database, have observed that showing Tanimoto scores higher than 0.9 with a metabolite, are 29.5 times more likely bind enzymes metabolizing considered ligands chosen randomly. RNA-seq data constrain GSMM it is possible obtain an estimation its distribution...
In this work, the effects of apolar, chlorinated, and polar organic solvents on activity structure glucose oxidase were theoretically experimentally investigated.
There is a clinical need for HIV protease inhibitors that can evade resistance mutations. One possible approach to designing such relies upon the crystallographic observation substrates of occupy rather constant region within binding site. In particular, it has been hypothesized which lie this will tend resist clinically relevant The present study offers first prospective evaluation hypothesis, via computational design predicted conform substrate envelope, followed by synthesis and against...
Abstract Crystallographic data show that various substrates of HIV protease occupy a remarkably uniform region within the binding site; this has been termed substrate envelope. It suggested an inhibitor fits envelope should tend to evade viral resistance because mutation reduces affinity will also reduce substrate, and hence decrease activity enzyme. Accordingly, inhibitors fit better be less susceptible clinically observed resistant mutations, since these must allow bind. The present study...
HI0719 belongs to a large family of highly conserved proteins with no definitive molecular function and is found in organisms ranging from bacteria humans. We describe the NMR structure HI0719, first solution for member this family. The overall fold similar crystal structures two homologues, YabJ Bacillus subtilis YjgF Escherichia coli, all three are that chorismate mutase, although there little sequence homology apparent functional connection. homotrimer distinct cavity located at subunit...
Modern drug discovery revolves around designing ligands that target the chosen biomolecule, typically proteins. For this, evaluation of affinities putative is crucial. This has given rise to a multitude dedicated computational and experimental methods are constantly being developed improved.
In order to detail the antiplasmodial effects of quinones (Q) and nitroaromatic compounds (ArNO2), we investigated their reduction mechanism by Plasmodium falciparum flavoenzyme type II NADH:ubiquinone oxidoreductase (PfNDH2). The reactivity Q ArNO2 (n = 29) follows a common trend exhibits parabolic dependence on single-electron potential (E71), albeit with significantly scattered data. similar E71 values increases lipophilicity. Quinones are reduced PfNDH2 in two-electron way, but way....
Abstract The ligand–protein docking algorithm based on the Mining Minima method has been substantially enhanced. First, basic is accelerated by: (1) adaptively determining extent of each energy well to help avoid previously discovered minima; (2) biasing search away from ligand positions at surface receptor prevent staying when large sampling regions are used; (3) quickly testing multiple different and orientations for conformation; (4) tuning source code increase computational efficiency....
The early stage of drug discovery is often based on selecting the highest affinity lead compound. To this end structural and energetic characterization binding reaction important. energetics can be resolved into enthalpic entropic contributions to Gibbs free energy. Most compound reactions are coupled absorption or release protons by protein A distinction between observed intrinsic parameters requires dissection protonation/deprotonation processes. Since only correlated with molecular...
A divide-and-conquer method by which an accurate static and induced multipole representation of the electrostatic potential a protein can be generated using ab initio electronic structure theory is presented. The applied to generation effective fragment (J. Chem. Phys. 1996, 105, 1968) for turkey ovomucoid third domain. Dipoles dipoles are necessary intraprotein electrostatics, as measured their effects on gas-phase proton affinities (PAs) amino acid residues lysine 55 (Lys55) tyrosine 20...