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Precechtelova J.,National Center for Biomolecular Research | Precechtelova J.,Masaryk University | Munzarova M.L.,National Center for Biomolecular Research | Munzarova M.L.,Masaryk University | And 7 more authors.
Journal of Chemical Theory and Computation | Year: 2013

This work addresses the question of the ability of the molecular dynamics-density functional theory (MD/DFT) approach to reproduce sequence trend in 31P chemical shifts (δP) in the backbone of nucleic acids. δP for [d(CGCGAATTCGCG)]2, a canonical B-DNA, have been computed using density functional theory calculations on model compounds with geometries cut out of snapshots of classical molecular dynamics (MD) simulations. The values of 31P chemical shifts for two distinct B-DNA subfamilies BI and BII, δP/BI and δP/BII, have been determined as averages over the BI and BII subparts of the MD trajectory. This has been done for various samplings of MD trajectory and for two sizes of both the model and the solvent embedding. For all of the combinations of trajectory sampling, model size, and embedding size, sequence dependence of δP/BI in the order of 0.4-0.5 ppm has been obtained. Weighted averages for individual 31P nuclei in the studied DNA double-helix have been calculated from δP/BI and δP/BII using BI and BII percentages from free MD simulations as well as from approaches employing NMR structural restraints. A good qualitative agreement is found between experimental sequence trends in δP and theoretical δP employing short (24 ns) MD run and BI, BII percentages determined by Hartmann et al. or via MD with the inclusion of NMR structural restraints. Theoretical δP exhibit a systematic offset of ca. 11 ppm and overestimation of trends by a factor of ca. 1.7. When scaled accordingly, theoretical δP/BI and δP/BII can be used to determine the expected percentage of BII to match the experimental value of δP. As evidenced by the calculations on snapshots from Car-Parrinello molecular dynamics, the systematic offsets of the theoretical δP obtained by MD/DFT approach result primarily from the unrealistic bond lengths employed by classical MD. The findings made in this work provide structure-δP relationships for possible use as NMR restraints and suggest that NMR calculations on MD snapshots can be in the future employed for the validation of newly developed force fields. © 2013 American Chemical Society. Source

Peterlik I.,Masaryk University | Peterlik I.,Brno University of Technology | Filipovic J.,Masaryk University | Filipovic J.,National Center for Biomolecular Research
IEEE Transactions on Industrial Electronics | Year: 2011

Haptic rendering is an important area of research that enables the user to employ haptic perception in human-computer interaction. An important motivation here is to use the human touch to study the behavior of various models. However, the high refresh rate needed for a stable haptic interaction on the one hand and the high-computational-cost characteristic for the simulation of numerous phenomena on the other hand represent a big issue. In this paper, an approach based on the distributed construction of configuration spaces is presented. The main idea behind this approach is to profit from employing a high-performance environment (e.g., computational grid) to overcome or at least moderate the high-frequency issue. The approach is presented using nonlinear deformation models, which are essential for realistic modeling of soft tissues. A distributed algorithm is presented, and its properties are evaluated quantitatively. © 2009 IEEE. Source

Pawlak T.,National Center for Biomolecular Research | Pawlak T.,Polish Academy of Sciences | Pawlak T.,Nicolaus Copernicus University | Munzarova M.L.,National Center for Biomolecular Research | And 4 more authors.
Journal of Chemical Theory and Computation | Year: 2011

Recently implemented hybrid density functional methods of calculating nuclear magnetic shielding using the two-component zeroth-order regular approximation approach (J. Phys. Chem. A2009, 113, 11495) have been employed for a series of compounds containing heavy transition-metal atoms. These include Pt2+, Pd2+, and Au3+ organometallics and metal complexes with azines, some of which exhibit interesting biological and catalytic activities. In this study we investigate the effects of geometry, exchange-correlation functional, solvent, and scalar relativistic and spin-orbit corrections on the nuclear magnetic shielding-mainly for 13C and 15N atoms connected to a heavy-atom center. Our calculations demonstrate that the B3LYP method using effective core potentials and a cc-pwCVTZ-PP/6-31G* basis set augmented with the polarizable continuum model of the dimethylsulfoxide solvent provides geometries for the complexes in question which are compatible with the experimental NMR results in terms of both the trends and the absolute values of the 13C shifts. The important role of the exact exchange admixture parameter for hybrid functionals based on B3LYP and PBE0 is investigated systematically for selected Pt2+ and Au3+ complexes. The 13C and 15N NMR chemical shifts are found to be best reproduced by using a B3LYP or PBE0 approach with 30% and 40-50% exact exchange admixtures for the Pt2+ and Au 3+ complexes, respectively. The spin-orbit contributions to the 15N NMR chemical shifts reflect metal-ligand bonding that is much more ionic for the Au3+ than for the Pt2+ complex. Finally, an optimized density functional method is applied to a series of transition-metal complexes to estimate the scope and the limitations of the current approach. © 2011 American Chemical Society. Source

Demo G.,Masaryk University | Horska V.,National Center for Biomolecular Research | Fliedrova B.,Academy of Sciences of the Czech Republic | Stepan J.,Masaryk University | And 4 more authors.
Glycobiology | Year: 2014

This study is focused on the analysis and mutagenesis of β-mannosidase from Bacteroides thetaiotaomicron with the aim of broadening its substrate specificity to 2-acetamido-2-deoxy-β-d-mannopyranosyl (β-ManNAc) derivatives. Various conformations ((4)C1, (4)H5 and (1)S5) of native and modified ligands were docked to the binding site of the protein to determine the most suitable conformation of sugars for further hydrolysis. Key amino acid residues were mutated in silico focusing on stabilizing the acetamido group of β-ManNAc as well as forming the oxazoline intermediate needed for hydrolysis. The results of large set of 5 ns molecular dynamic simulations showed that the majority of the active site residues are involved in substrate interaction and do not exhibit a higher flexibility except for Asn178. Mutations of Asn178 to alanine and Asp199 to serine could lead to a stabilization of the acetamido group in the binding site. So far, in vitro mutagenesis and the screen of a large variety of biological sources were unable to extend β-mannosidase's activity to include β-ManNAc derivatives. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Source

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