Daniel Svozil | Institute of Chemical Technology Prague (original) (raw)
Papers by Daniel Svozil
The Journal of …, Jan 1, 2008
The hepatitis delta virus (HDV) ribozyme is an RNA motif embedded in human pathogenic HDV RNA. Pr... more The hepatitis delta virus (HDV) ribozyme is an RNA motif embedded in human pathogenic HDV RNA. Previous experimental studies have established that the active-site nucleotide C75 is essential for self-cleavage of the ribozyme, although its exact catalytic role in the process remains debated. Structural data from X-ray crystallography generally indicate that C75 acts as the general base that initiates catalysis by deprotonating the 2′-OH nucleophile at the cleavage site, while a hydrated magnesium ion likely protonates the 5′-oxygen leaving group. In contrast, some mechanistic studies support the role of C75 acting as general acid and thus being protonated before the reaction. We report combined quantum chemical/molecular mechanical calculations for the C75 general base pathway, utilizing the available structural data for the wild type HDV genomic ribozyme as a starting point. Several starting configurations differing in magnesium ion placement were considered and both one-dimensional and two-dimensional potential energy surface scans were used to explore plausible reaction paths. Our calculations show that C75 is readily capable of acting as the general base, in concert with the hydrated magnesium ion as the general acid. We identify a most likely position for the magnesium ion, which also suggests it acts as a Lewis acid. The calculated energy barrier of the proposed mechanism, ∼20 kcal/mol, would lower the reaction barrier by ∼15 kcal/mol compared with the uncatalyzed reaction and is in good agreement with experimental data.
Journal of Analytical …, Jan 1, 2000
Univariate and multivariate (partial least squares 1, PLS1) calibration techniques are compared f... more Univariate and multivariate (partial least squares 1, PLS1) calibration techniques are compared for the determination of Pt, Pd and Rh in a complex sample matrix. The univariate techniques utilised either pure standards, pure standards with interelement correction factors applied, or matrix matched standards. Univariate calibration yielded relative root mean square errors (RRMSEs) of prediction for Pt, Pd and Rh of 19, 15, and 54% and 13, 18, and 88% for test solutions and real samples, respectively. Univariate calibration with matrix matching proved the most accurate method with RRMSEs for Pt, Pd and Rh of 2.5, 3.7 and 2.4% for a series of synthetic test solutions, and 12, 2.3 and 8.0% for real samples, respectively. In comparison, the multivariate calibration method yielded relative root mean errors for Pt, Pd and Rh of 5.8, 3.0 and 3.5% in the test solutions, and 32, 7.4 and 76% in the real samples. The relative error for the matrix matching and PLS1 techniques was dependent upon analyte concentration.
The Journal of …, Jan 1, 2008
The anionic sugar-phosphate backbone of nucleic acids substantially contributes to their structur... more The anionic sugar-phosphate backbone of nucleic acids substantially contributes to their structural flexibility. To model nucleic acid structure and dynamics correctly, the potentially sampled substates of the sugar-phosphate backbone must be properly described. However, because of the complexity of the electronic distribution in the nucleic acid backbone, its representation by classical force fields is very challenging. In this work, the three-dimensional potential energy surfaces with two independent variables corresponding to rotations around the R and γ backbone torsions are studied by means of high-level ab initio methods (B3LYP/ 6-31+G*, MP2/6-31+G*, and MP2 complete basis set limit levels). The ability of the AMBER ff99 [Wang, J. M.; Cieplak, P.; Kollman, P. A. J. Comput. Chem. 2000, 21, 1049-1074] and parmbsc0 [Perez, A.; Marchan, I.; Svozil, D.; Š poner, J.; Cheatham, T. E.; Laughten, C. A.; Orozco, M. Biophys. J. 2007, 92, [3817][3818][3819][3820][3821][3822][3823][3824][3825][3826][3827][3828][3829] force fields to describe the various R/γ conformations of the DNA backbone accurately is assessed by comparing the results with those of ab initio quantum chemical calculations. Two model systems differing in structural complexity were used to describe the R/γ energetics. The simpler one, SPM, consisting of a sugar and methyl group linked through a phosphodiester bond was used to determine higher-order correlation effects covered by the CCSD(T) method. The second, more complex model system, SPSOM, includes two deoxyribose residues (without the bases) connected via a phosphodiester bond. It has been shown by means of a natural bond orbital analysis that the SPSOM model provides a more realistic representation of the hyperconjugation network along the C5′-O5′-P-O3′-C3′ linkage. However, we have also shown that quantum mechanical investigations of this model system are nontrivial because of the complexity of the SPSOM conformational space. A comparison of the ab initio data with the ff99 potential energy surface clearly reveals an incorrect ff99 force-field description in the regions where the γ torsion is in the trans conformation. An explanation is proposed for why the R/γ flips are eliminated so successfully when the parmbsc0 force-field modification is used.
Collection of Czechoslovak …, Jan 1, 2004
Journal of chemical …, Jan 1, 1997
A three-layer feed-forward neural network was used for the prediction of the polarity/polarizabil... more A three-layer feed-forward neural network was used for the prediction of the polarity/polarizability parameter π 2 H . A simulated annealing algorithm was used to minimize the error at the neural network output. Descriptors related to the structure of the compounds were calculated as the input vector. The Kohonen neural network was used to split the data set into training and testing sets. The results obtained from the neural network were compared with the MLRA results.
Journal of electroanalytical chemistry, Jan 1, 1995
Journal of chemical …, Jan 1, 1995
... (6) Cherqaoui, D.; Villemin, D.; Mesbah, A,; Cence, JM; KvasniEka, V. J. Use of a Neural Netw... more ... (6) Cherqaoui, D.; Villemin, D.; Mesbah, A,; Cence, JM; KvasniEka, V. J. Use of a Neural Network to determine the Normal Boiling Points SVOZIL ET AL. ... (10) Harary, F. Graph Theop; Addison Wesley: Reading, MA, 1969. ... (14) Dayhoff, J. Neural Nerwork Architectures; Van ...
Nucleic acids …, Jan 1, 2008
The geometry of the phosphodiester backbone was analyzed for 7739 dinucleotides from 447 selected... more The geometry of the phosphodiester backbone was analyzed for 7739 dinucleotides from 447 selected crystal structures of naked and complexed DNA. Ten torsion angles of a near-dinucleotide unit have been studied by combining Fourier averaging and clustering. Besides the known variants of the A-, B- and Z-DNA forms, we have also identified combined A + B backbone-deformed conformers, e.g. with α/γ switches, and a few conformers with a syn orientation of bases occurring e.g. in G-quadruplex structures. A plethora of A- and B-like conformers show a close relationship between the A- and B-form double helices. A comparison of the populations of the conformers occurring in naked and complexed DNA has revealed a significant broadening of the DNA conformational space in the complexes, but the conformers still remain within the limits defined by the A- and B- forms. Possible sequence preferences, important for sequence-dependent recognition, have been assessed for the main A and B conformers by means of statistical goodness-of-fit tests. The structural properties of the backbone in quadruplexes, junctions and histone-core particles are discussed in further detail.
Chemometrics and intelligent …, Jan 1, 1997
Basic definitions concerning the multi-layer feed-forward neural networks are given. The back-pro... more Basic definitions concerning the multi-layer feed-forward neural networks are given. The back-propagation training algorithm is explained. Partial derivatives of the objective function with respect to the weight and threshold coefficients are derived. These derivatives are valuable for an adaptation process of the considered neural network. Training and generalisation of multi-layer feed-forward neural networks are discussed. Improvements of the standard back-propagation algorithm are reviewed. Example of the use of multi-layer feed-forward neural networks for prediction of carbon-13 NMR chemical shifts of alkanes is given. Further applications of neural networks in chemistry are reviewed. Advantages and disadvantages of multilayer feed-forward neural networks are discussed. 0 1997 Elsevier Science B.V.
![Research paper thumbnail of Refinement of the AMBER force field for nucleic acids: improving the description of [alpha]/[gamma] conformers](https://attachments.academia-assets.com/51016046/thumbnails/1.jpg)
](Biophysical journal, Jan 1, 2007
We present here the parmbsc0 force field, a refinement of the AMBER parm99 force field, where emp... more We present here the parmbsc0 force field, a refinement of the AMBER parm99 force field, where emphasis has been made on the correct representation of the a/g concerted rotation in nucleic acids (NAs). The modified force field corrects overpopulations of the a/g ¼ (g1,t) backbone that were seen in long (more than 10 ns) simulations with previous AMBER parameter sets (parm94-99). The force field has been derived by fitting to high-level quantum mechanical data and verified by comparison with very high-level quantum mechanical calculations and by a very extensive comparison between simulations and experimental data. The set of validation simulations includes two of the longest trajectories published to date for the DNA duplex (200 ns each) and the largest variety of NA structures studied to date (15 different NA families and 97 individual structures). The total simulation time used to validate the force field includes near 1 ms of state-of-the-art molecular dynamics simulations in aqueous solution.
The Journal of …, Jan 1, 2008
The hepatitis delta virus (HDV) ribozyme is an RNA motif embedded in human pathogenic HDV RNA. Pr... more The hepatitis delta virus (HDV) ribozyme is an RNA motif embedded in human pathogenic HDV RNA. Previous experimental studies have established that the active-site nucleotide C75 is essential for self-cleavage of the ribozyme, although its exact catalytic role in the process remains debated. Structural data from X-ray crystallography generally indicate that C75 acts as the general base that initiates catalysis by deprotonating the 2′-OH nucleophile at the cleavage site, while a hydrated magnesium ion likely protonates the 5′-oxygen leaving group. In contrast, some mechanistic studies support the role of C75 acting as general acid and thus being protonated before the reaction. We report combined quantum chemical/molecular mechanical calculations for the C75 general base pathway, utilizing the available structural data for the wild type HDV genomic ribozyme as a starting point. Several starting configurations differing in magnesium ion placement were considered and both one-dimensional and two-dimensional potential energy surface scans were used to explore plausible reaction paths. Our calculations show that C75 is readily capable of acting as the general base, in concert with the hydrated magnesium ion as the general acid. We identify a most likely position for the magnesium ion, which also suggests it acts as a Lewis acid. The calculated energy barrier of the proposed mechanism, ∼20 kcal/mol, would lower the reaction barrier by ∼15 kcal/mol compared with the uncatalyzed reaction and is in good agreement with experimental data.
Journal of Analytical …, Jan 1, 2000
Univariate and multivariate (partial least squares 1, PLS1) calibration techniques are compared f... more Univariate and multivariate (partial least squares 1, PLS1) calibration techniques are compared for the determination of Pt, Pd and Rh in a complex sample matrix. The univariate techniques utilised either pure standards, pure standards with interelement correction factors applied, or matrix matched standards. Univariate calibration yielded relative root mean square errors (RRMSEs) of prediction for Pt, Pd and Rh of 19, 15, and 54% and 13, 18, and 88% for test solutions and real samples, respectively. Univariate calibration with matrix matching proved the most accurate method with RRMSEs for Pt, Pd and Rh of 2.5, 3.7 and 2.4% for a series of synthetic test solutions, and 12, 2.3 and 8.0% for real samples, respectively. In comparison, the multivariate calibration method yielded relative root mean errors for Pt, Pd and Rh of 5.8, 3.0 and 3.5% in the test solutions, and 32, 7.4 and 76% in the real samples. The relative error for the matrix matching and PLS1 techniques was dependent upon analyte concentration.
The Journal of …, Jan 1, 2008
The anionic sugar-phosphate backbone of nucleic acids substantially contributes to their structur... more The anionic sugar-phosphate backbone of nucleic acids substantially contributes to their structural flexibility. To model nucleic acid structure and dynamics correctly, the potentially sampled substates of the sugar-phosphate backbone must be properly described. However, because of the complexity of the electronic distribution in the nucleic acid backbone, its representation by classical force fields is very challenging. In this work, the three-dimensional potential energy surfaces with two independent variables corresponding to rotations around the R and γ backbone torsions are studied by means of high-level ab initio methods (B3LYP/ 6-31+G*, MP2/6-31+G*, and MP2 complete basis set limit levels). The ability of the AMBER ff99 [Wang, J. M.; Cieplak, P.; Kollman, P. A. J. Comput. Chem. 2000, 21, 1049-1074] and parmbsc0 [Perez, A.; Marchan, I.; Svozil, D.; Š poner, J.; Cheatham, T. E.; Laughten, C. A.; Orozco, M. Biophys. J. 2007, 92, [3817][3818][3819][3820][3821][3822][3823][3824][3825][3826][3827][3828][3829] force fields to describe the various R/γ conformations of the DNA backbone accurately is assessed by comparing the results with those of ab initio quantum chemical calculations. Two model systems differing in structural complexity were used to describe the R/γ energetics. The simpler one, SPM, consisting of a sugar and methyl group linked through a phosphodiester bond was used to determine higher-order correlation effects covered by the CCSD(T) method. The second, more complex model system, SPSOM, includes two deoxyribose residues (without the bases) connected via a phosphodiester bond. It has been shown by means of a natural bond orbital analysis that the SPSOM model provides a more realistic representation of the hyperconjugation network along the C5′-O5′-P-O3′-C3′ linkage. However, we have also shown that quantum mechanical investigations of this model system are nontrivial because of the complexity of the SPSOM conformational space. A comparison of the ab initio data with the ff99 potential energy surface clearly reveals an incorrect ff99 force-field description in the regions where the γ torsion is in the trans conformation. An explanation is proposed for why the R/γ flips are eliminated so successfully when the parmbsc0 force-field modification is used.
Collection of Czechoslovak …, Jan 1, 2004
Journal of chemical …, Jan 1, 1997
A three-layer feed-forward neural network was used for the prediction of the polarity/polarizabil... more A three-layer feed-forward neural network was used for the prediction of the polarity/polarizability parameter π 2 H . A simulated annealing algorithm was used to minimize the error at the neural network output. Descriptors related to the structure of the compounds were calculated as the input vector. The Kohonen neural network was used to split the data set into training and testing sets. The results obtained from the neural network were compared with the MLRA results.
Journal of electroanalytical chemistry, Jan 1, 1995
Journal of chemical …, Jan 1, 1995
... (6) Cherqaoui, D.; Villemin, D.; Mesbah, A,; Cence, JM; KvasniEka, V. J. Use of a Neural Netw... more ... (6) Cherqaoui, D.; Villemin, D.; Mesbah, A,; Cence, JM; KvasniEka, V. J. Use of a Neural Network to determine the Normal Boiling Points SVOZIL ET AL. ... (10) Harary, F. Graph Theop; Addison Wesley: Reading, MA, 1969. ... (14) Dayhoff, J. Neural Nerwork Architectures; Van ...
Nucleic acids …, Jan 1, 2008
The geometry of the phosphodiester backbone was analyzed for 7739 dinucleotides from 447 selected... more The geometry of the phosphodiester backbone was analyzed for 7739 dinucleotides from 447 selected crystal structures of naked and complexed DNA. Ten torsion angles of a near-dinucleotide unit have been studied by combining Fourier averaging and clustering. Besides the known variants of the A-, B- and Z-DNA forms, we have also identified combined A + B backbone-deformed conformers, e.g. with α/γ switches, and a few conformers with a syn orientation of bases occurring e.g. in G-quadruplex structures. A plethora of A- and B-like conformers show a close relationship between the A- and B-form double helices. A comparison of the populations of the conformers occurring in naked and complexed DNA has revealed a significant broadening of the DNA conformational space in the complexes, but the conformers still remain within the limits defined by the A- and B- forms. Possible sequence preferences, important for sequence-dependent recognition, have been assessed for the main A and B conformers by means of statistical goodness-of-fit tests. The structural properties of the backbone in quadruplexes, junctions and histone-core particles are discussed in further detail.
Chemometrics and intelligent …, Jan 1, 1997
Basic definitions concerning the multi-layer feed-forward neural networks are given. The back-pro... more Basic definitions concerning the multi-layer feed-forward neural networks are given. The back-propagation training algorithm is explained. Partial derivatives of the objective function with respect to the weight and threshold coefficients are derived. These derivatives are valuable for an adaptation process of the considered neural network. Training and generalisation of multi-layer feed-forward neural networks are discussed. Improvements of the standard back-propagation algorithm are reviewed. Example of the use of multi-layer feed-forward neural networks for prediction of carbon-13 NMR chemical shifts of alkanes is given. Further applications of neural networks in chemistry are reviewed. Advantages and disadvantages of multilayer feed-forward neural networks are discussed. 0 1997 Elsevier Science B.V.
Biophysical journal, Jan 1, 2007
We present here the parmbsc0 force field, a refinement of the AMBER parm99 force field, where emp... more We present here the parmbsc0 force field, a refinement of the AMBER parm99 force field, where emphasis has been made on the correct representation of the a/g concerted rotation in nucleic acids (NAs). The modified force field corrects overpopulations of the a/g ¼ (g1,t) backbone that were seen in long (more than 10 ns) simulations with previous AMBER parameter sets (parm94-99). The force field has been derived by fitting to high-level quantum mechanical data and verified by comparison with very high-level quantum mechanical calculations and by a very extensive comparison between simulations and experimental data. The set of validation simulations includes two of the longest trajectories published to date for the DNA duplex (200 ns each) and the largest variety of NA structures studied to date (15 different NA families and 97 individual structures). The total simulation time used to validate the force field includes near 1 ms of state-of-the-art molecular dynamics simulations in aqueous solution.