A5045570505- Protein Structure and Dynamics
- Spectroscopy and Quantum Chemical Studies
- DNA and Nucleic Acid Chemistry
- Computational Drug Discovery Methods
- Protein Interaction Studies and Fluorescence Analysis
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Biochemical and Molecular Research
- Monoclonal and Polyclonal Antibodies Research
- HIV/AIDS drug development and treatment
- Free Radicals and Antioxidants
- Microfluidic and Capillary Electrophoresis Applications
- Protein purification and stability
- Molecular spectroscopy and chirality
- Pesticide Exposure and Toxicity
- Various Chemistry Research Topics
- HIV Research and Treatment
- Electrostatics and Colloid Interactions
- Chemical Reaction Mechanisms
- Adenosine and Purinergic Signaling
- Genetics, Bioinformatics, and Biomedical Research
- Thermodynamic properties of mixtures
- Molecular Junctions and Nanostructures
- Chemical and Physical Properties in Aqueous Solutions
University of Warsaw
2015-2024
Nicolaus Copernicus University
2019
Institute of Experimental Physics of the Slovak Academy of Sciences
2014
Max Planck Institute for Biophysical Chemistry
1988-2009
University of California, San Diego
1995-1998
University of Iowa
1998
National Institute of Standards and Technology
1998
University of Houston
1994-1997
Biotechnology Institute
1997
Max Planck Society
1988-1993
Although validation studies show that theoretical models for predicting the pKas of ionizable groups in proteins are increasingly accurate, a number important questions remain: (1) What factors limit accuracy current models? (2) How can conformational flexibility best be accounted for? (3) Will use solution structures calculations, rather than crystal structures, improve computed pKas? and (4) Why does accurate prediction protein seem to require high dielectric constant assigned interior?...
Abstract Relationships between protein structure and ionization of carboxyl groups were investigated in 24 proteins known for which 115 aspartate 97 glutamate pK a values are known. Mean aspartates glutamates ≤ 3.4 (±1.0) 4.1 (±0.8), respectively. For aspartates, mean 3.9 3.1 (±0.9) acidic (pI < 5) basic > 8) proteins, respectively, while approximately 4.2 proteins. Burial leads to dispersion values: solvent‐exposed show narrow distributions buried range from 2 6.7. Calculated...
A convenient computational approach for the calculation of p Kas ionizable groups in a protein is described. The method uses detailed models charges both neutral and ionized form each group. full derivation theoretical framework presented, as are details its implementation UHBD program. Application to four proteins whose crystal structures known shows that charge model improves agreement with experimentally determined pKas when low dielectric constant assumed, relative results simpler...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe nature of protein dipole moments: experimental and calculated permanent .alpha.-chymotrypsinJan Antosiewicz Dietmar PorschkeCite this: Biochemistry 1989, 28, 26, 10072–10078Publication Date (Print):December 1, 1989Publication History Published online1 May 2002Published inissue 1 December 1989https://pubs.acs.org/doi/10.1021/bi00452a029https://doi.org/10.1021/bi00452a029research-articleACS PublicationsRequest reuse permissionsArticle...
2D-NMR experiments were used to determine the pKa values ranging from 8.0 >/=11.1 of seven basic residues in turkey ovomucoid third domain (OMTKY3) and compared predicted as described by Antosiewicz et al. [(1996) Biochemistry 35, 7819-7833]. Lys 13, 29, 34 previously attributed with increasing acidity numerous acidic [Schaller, W., Robertson, A. D. (1995) 34, 4714-4723]. These interactions expected raise those groups; however, 13 are less than model compound values. The other greater and,...
Abstract The aspartyl dyad of free HIV‐1 protease has apparent pK a s ∼3 and ∼6, but recent NMR studies indicate that the is fixed in doubly protonated form over wide pH range when cyclic urea inhibitors are bound, monoprotonated inhibitor KNI‐272 bound. We present computations measurements related to these changes protonation thermodynamic linkage between inhibition. Poisson‐Boltzmann model electrostatics used compute enzyme complexes with four different inhibitors. calculations done two...
Two-dimensional homo- and heteronuclear nuclear magnetic resonance (NMR) spectroscopy was used to determine pKa values for all of the acidic residues in B1 B2 immunoglobulin G- (IgG-) binding domains protein G. Due stability G over a wide pH range, estimates ionization constants were also obtained some basic residues. These experimentally determined compared with calculated from both X-ray NMR-derived structures using UHBD algorithm [Antosiewicz, J., et al. (1994) J. Mol. Biol. 238,...
Molecular dynamics (MD) simulations with implicit solvent and variable protonation states for titratable residues at constant pH are performed a short peptide derived from ovomucoid third domain (OMTKY3), acetyl-Ser-Asp-Asn-Lys-Thr-Tyr-Gly-amide (residues 26--32 of OMTKY3). Nuclear magnetic resonance (NMR) measurements indicate that the ${\mathrm{pK}}_{a}$ Asp is 3.6. However, if charge on Lys neutralized by acetylation, then $p{\mathrm{K}}_{a}$ 4.0. These...
A recent experimental study of human acetylcholinesterase has shown that the mutation surface acidic residues little effect on rate constant for hydrolysis acetylthiocholine. It was concluded, this basis, reaction is not diffusion controlled and electrostatic steering plays only a minor role in determining rate. Here we examine issue through Brownian dynamics simulations Torpedo californica which homologous with those mutated enzyme are artificially neutralized. The computed effects...
The electrostatic steering of charged ligands toward the active site Torpedo californica acetylcholinesterase is investigated by Brownian dynamics simulations wild type enzyme and several mutated forms, in which some normally residues are neutralized. reveal that total ligand influx through a surface 42 Å radius centered monomer separated from protein I-14 not significantly influenced interactions. Electrostatic effects visible for encounters with 32 radius, partially hidden inside protein,...
Multiconfiguration thermodynamic integration was used to determine the relative binding strength of tacrine and 6-chlorotacrine by Torpedo californica acetylcholinesterase. 6-Chlorotacrine appears be bound stronger 0.7+/-0.4 kcal/mol than unsubstituted when active site triad residue His-440 is deprotonated. This result in excellent agreement with experimental inhibition data on electric eel Electrostatic Poisson-Boltzmann calculations confirm that order strength, resulting deltaG -2.9 -3.3...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTVolume correction for bead model simulations of rotational friction coefficients macromoleculesJan Antosiewicz and Dietmar PorschkeCite this: J. Phys. Chem. 1989, 93, 13, 5301–5305Publication Date (Print):June 1, 1989Publication History Published online1 May 2002Published inissue 1 June 1989https://pubs.acs.org/doi/10.1021/j100350a051https://doi.org/10.1021/j100350a051research-articleACS PublicationsRequest reuse permissionsArticle...
Brownian dynamics simulations of the encounter kinetics between active site wild-type and Glu199 mutant Torpedo californica acetylcholinesterase (TcAChE) with a charged substrate were performed. In addition, ab initio quantum chemical calculations using 3-21G basis set undertaken to probe energetics transformation Michaelis complex into covalently bound tetrahedral intermediate various models Glu199Gln sites. The predicted about factor 32 reduction in rate formation upon mutation showed that...
This paper explores the dependence of molecular dynamics (MD) trajectory a protein molecule on titration state assigned to molecule. Four 100-ps MD trajectories bovine pancreatic trypsin inhibitor (BPTI) were generated, starting from two different structures, each which was held in charge states. The structures X-ray crystal structure and one solution determined by NMR, states differed only ionization N terminus. Although it is evident that simulations too short sample fully equilibrium...