Co-reporter:Mingqiong Tong, Qing Wang, Yan Wang and Guangju Chen
RSC Advances 2015 vol. 5(Issue 81) pp:65798-65810
Publication Date(Web):27 Jul 2015
DOI:10.1039/C5RA11234F
We carried out conventional molecular dynamics simulations, targeted molecular dynamics simulations and energy calculations for the two states (AFF-D9k-N′ and AFF-D9k-N) of the alternate frame folding (AFF) calbindin-D9k protein and their conformational transition in the Ca2+-free form to address the dynamical transition mechanism from AFF-D9k-N′ to AFF-D9k-N states. We found that the structural characteristics of the two stable AFF-D9k-N′ and AFF-D9k-N states present the coupled conformations of mutually exclusive folding. The transition from AFF-D9k-N′ to AFF-D9k-N states may occur via two transition states and an intermediate with the first rate-controlling barrier of 4.7 kcal mol−1 and the second barrier of 1.7 kcal mol−1. These results showed that the conformational transition pathway from AFF-D9k-N′ to AFF-D9k-N is energetically feasible due to the low rate-controlling barrier. Moreover, the stabilities of the AFF-D9k-N′ and AFF-D9k-N conformations calculated by the MM_PBSA method are consistent with the available experimental result. The transition mechanism involves the relative movements of the two mutually exclusive folding regions, EF2 and EF2′, and their coupled folding-unfolding. The crucial mediation of the deformation of EF1 hand located at the middle of the AFF calbindin-D9k protein plays a key role in this transition process. The correlation analysis revealed the allosteric communications between the EF2′ and EF2 regions via the mediation of the EF1 hand during the transition of AFF-D9k-N′ to AFF-D9k-N.
Co-reporter:Chaoqun Li, Na Ma, Yaru Wang, Yan Wang, and Guangju Chen
The Journal of Physical Chemistry B 2014 Volume 118(Issue 5) pp:1273-1287
Publication Date(Web):January 24, 2014
DOI:10.1021/jp411111g
The positive cooperativity of the Kemptide substrate or the ATP molecule with the PKA catalytic subunit has been studied by dynamics simulations and free energy calculations on a series of binary and ternary models. The results revealed that the first ATP binding to the PKA catalytic subunit is energetically favorable for the successive Kemptide binding, confirming the positive cooperativity. The key residues Thr51, Glu170, and Phe187 in PKA contributing to the positive cooperativity have been found. The binding of ATP to PKA induces the positive cooperativity through one direct allosteric communication network in PKA from the ATP binding sites in the catalytic loop of the large lobe to the Kemptide binding sites in the activation segment of the large lobe, two indirect ones from those in the glycine-rich loop and the β3 strand of the small lobe, and from those in the catalytic loop to those in the activation segment via the αF helix media. The Tyr204Ala mutation in the activation segment of PKA causes both the decoupling of the cooperativity and the disruption of the corresponding allosteric network through the αF helix media.
Co-reporter:Mingqiong Tong, Zhenfen Yin, Yan Wang, Guangju Chen
International Journal of Hydrogen Energy 2013 Volume 38(Issue 35) pp:15285-15294
Publication Date(Web):22 November 2013
DOI:10.1016/j.ijhydene.2013.09.097
•The dehydrogenation of BH3NH3 on the Pd2/MgO surface can be the concerted and stepwise.•BH3NH3 on the Pd4/MgO surface can be dehydrogenated in the stepwise way.•BH3NH3 was predicted easily to release H2 on both the Pd2/MgO and Pd4/MgO surfaces.•The barrier heights can change with the size of Pd clusters on the MgO surface.The dehydrogenation of ammonia borane (BH3NH3) catalyzed by Pd supported on an MgO(100) surface was investigated using the DFT/UB3LYP method and an embedded cluster model. We found that BH3NH3 molecules can be initially adsorbed on 2-Pd atom clusters on the MgO surface (Pd2/MgO) in two different configurations, and on 4-Pd atom clusters (Pd4/MgO) in one configuration. One of the two BH3NH3–Pd2/MgO configurations can dehydrogenate in a concerted pathway with a forward free energy barrier of 16.5 kcal/mol, and the other in a stepwise mechanism with forward barriers of 11.1 and 9.4 kcal/mol, respectively. However, only a stepwise dehydrogenation pathway was found for the single BH3NH3–Pd4/MgO configuration, with a rate-controlling barrier of 12.6 kcal/mol. These results suggest that the BH3NH3 dehydrogenation mechanism and reaction barrier height can change with the size of the Pd clusters on the MgO(100) surface.
Co-reporter:Chaoqun Li;Yaru Wang;Guangju Chen
Journal of Molecular Recognition 2013 Volume 26( Issue 11) pp:556-567
Publication Date(Web):
DOI:10.1002/jmr.2300
We carried out molecular dynamics simulations and free energy calculations for a series of ternary and diplex models for the HipA protein, HipB dimer, and DNA molecule to address the mechanism of HipA sequestration and the binding order of events from apo HipB/HipA to 2HipA + HipB dimer + DNA complex. The results revealed that the combination of DNA with the HipB dimer is energetically favorable for the combination of HipB dimer with HipA protein. The binding of DNA to HipB dimer induces a long-range allosteric communication from the HipB2-DNA interface to the HipA–HipB2 interface, which involves the closeness of α1 helices of HipB dimer to HipA protein and formations of extra hydrogen bonds in the HipA–HipB2 interface through the extension of α2/3 helices in the HipB dimer. These simulated results suggested that the DNA molecule, as a regulative media, modulates the HipB dimer conformation, consequently increasing the interactions of HipB dimer with the HipA proteins, which explains the mechanism of HipA sequestration reported by the previous experiment. Simultaneously, these simulations also explored that the thermodynamic binding order in a simulated physiological environment, that is, the HipB dimer first bind to DNA to form HipB dimer + DNA complex, then capturing strongly the HipA proteins to form a ternary complex, 2HipA + HipB dimer + DNA, for sequestrating HipA in the nucleoid. Copyright © 2013 John Wiley & Sons, Ltd.
Co-reporter:Zhenfen Yin, Chaoqun Li, Yanwei Su, Yongfei Liu, Yan Wang, Guangju Chen
Chemical Physics 2012 Volume 395() pp:108-114
Publication Date(Web):20 February 2012
DOI:10.1016/j.chemphys.2011.08.002
Abstract
The stepwise and concerted reaction mechanisms of NO with CO on Pd1 atom and Pd4 cluster adsorbed on the MgO surface have been studied by using the DFT/B3LYP method with the embedded cluster model. The reaction barriers have been calculated by using the IMOMO method at the CCSD level. The results suggest that the rate-controlling step barrier of the NO dissociation on the supported Pd4 cluster for the stepwise reaction mechanism is about 57 kcal/mol and lower by about 33 kcal/mol than that on the single supported Pd atom. However, the concerted reaction pathways on the single supported Pd atom and four supported Pd atoms are energetically unfavorable with the barriers of about 98 kcal/mol and 71 kcal/mol, respectively. Compared to the concerted reaction mechanism, the stepwise reaction mechanism of NO + CO is a possible pathway of CO2 molecule formation on the supported Pd catalysts.
Co-reporter:Yaru Wang;Yanyan Zhu;Guangju Chen
Journal of Molecular Recognition 2011 Volume 24( Issue 6) pp:981-994
Publication Date(Web):
DOI:10.1002/jmr.1146
In the present study, the molecular dynamics simulation technique is employed to investigate the hydrogen abstraction possibility from sugar of DNA in two designed complexes of copper-based chemical nuclease [Cu(BPA)]2+ bis(2-pyridylmethyl) amine (BPA) or [Cu(IDB)]2+ N,N-bis(2-benzimidazolylmethyl) amine (IDB) bound to the zinc finger protein Tramtrack (TTK). The simulated results show that each of the designed complexes can form a stable conformation within 30 ns of simulation time with the substrate OOH− and an 18-base pair (bp) DNA segment and is located in the major groove of the DNA segment. The active terminal O atom of the OOH− substrate is found in close proximity to the target C2′H, C3′H, C4′H or C5′H proton of the DNA in TTK + [Cu(BPA)OOH]+ + DNA or TTK + [Cu(IDB)OOH]+ + DNA complex, which is crucial to propose the hydrogen abstraction possibility that is responsible for the DNA cleavage. The positions of copper-based chemical nucleases bound to TTK may substantially influence the hydrogen abstraction possibility. The structures and sizes of ligands in copper-based nucleases are also found to have influence on the order of difficulty of the hydrogen abstraction from the sugars of DNA. Copyright © 2011 John Wiley & Sons, Ltd.
Co-reporter:Yongfei Liu;Guangju Chen
Journal of Molecular Modeling 2011 Volume 17( Issue 5) pp:1061-1068
Publication Date(Web):2011 May
DOI:10.1007/s00894-010-0809-2
The structures and energy properties for Agn (n = 1-8) metal clusters adsorbed on the perfect and oxygen vacancy MgO surfaces have been studied by using the DFT/UB3LYP method with an embedded cluster model. The nucleation and mobility model for the Agn (n = 1-8) clusters on the perfect and oxygen vacancy MgO(100) surfaces was investigated. The results show that the Ag atoms locate initially at the surface oxygen vacancy sites; then, with the growth of Ag cluster sizes, the large Ag clusters move possibly out of the vacancy sites by a rolling model, and diffuse on the MgO surface under a certain temperature condition. The relative energies needed for moving out of the oxygen vacancy region for the adsorbed Agn clusters with the rolling model have been predicted. The even-odd oscillation behaviors for the cohesive energies, nucleation energies, first ionization potentials and HOMO-LUMO gaps of the adsorbed Agn clusters with the variation of cluster sizes have also been discussed.
Co-reporter:Hongwei Yue;Yanyan Zhu;Guangju Chen
BMC Structural Biology 2010 Volume 10( Issue 1) pp:
Publication Date(Web):2010 December
DOI:10.1186/1472-6807-10-35
Copper nucleases as a famous class of artificial metallonucleases have attracted considerable interest in relation to their diverse potentials not only as therapeutic agents but also in genomic researches. Copper nucleases present high efficient oxidative cleavage of DNA, in which DNA strand scission occurs generally after hydrogen atom abstracted from a sugar moiety. In order to achieve the selective cleavage of DNA sequences by copper nucleases, the DNA specific recognition agents of the Dervan-type hairpin and cyclic polyamides can be considered as proper carriers of copper nucleases. Investigation of the DNA cleavage selectivity of copper nucleases assisted by the hairpin and cyclic polyamides at the molecular level has not yet been elucidated.We carried out a series of molecular dynamics simulations for the nuclease [Cu(BPA)]2+ or [Cu(IDB)]2+ bound to the hairpin/cyclic polyamide and associated with DNA to investigate the selective DNA cleavage properties of Cu(II)-based artificial nucleases. The simulated results demonstrate that the DNA cleavage selectivity of the two nucleases assisted by the hairpin polyamide is improved efficiently. The [Cu(BPA)]2+ or [Cu(IDB)]2+ nuclease with a substrate OOH- bound to the hairpin polyamide can be stably located at the minor groove of DNA, and possibly abstracts H atom from the sugar of DNA. However, the DNA cleavage properties of the two nucleases assisted by the cyclic polyamide are significantly poor due to the rigidity of linking region between the cyclic polyamide and nuclease. With introduction of the flexible linker -CH2CH2CH2NH2, the modified cyclic polyamide can assist the two copper nucleases to improve the selective DNA cleavage properties efficiently.A flexible linker and a proper binding site of the polyamide-type recognition agents play an important role in improving the DNA cleavage selectivity of copper nucleases. Current investigations provide an insight into the DNA cleavage specificities of chemical nucleases assisted by an appropriate nucleic acid recognition agent.
Co-reporter:Yanyan Zhu;Guangju Chen;Chang-Guo Zhan
Theoretical Chemistry Accounts 2009 Volume 122( Issue 3-4) pp:167-178
Publication Date(Web):2009 March
DOI:10.1007/s00214-008-0496-6
We present the theoretical evaluation of new AMBER force field parameters for 12 copper-based nucleases with bis(2-pyridylmethyl) amine, 2,2′-dipyridylamine, imidazole, N,N-bis(2-benzimidazolylmethyl) amine and their derivative ligands based on first-principles electronic structure calculations at the B3LYP level of theory. A three-point approach was developed to accurately and efficiently evaluate the force field parameters for the copper-based nucleases with the ligands. The protocol of RESP atomic charges has been used to calculate the atomic charge distributions of the studied copper-based nucleases. The evaluated force field parameters and RESP atomic charges have been successfully applied in the testing molecular mechanics calculations and molecular dynamics simulations on the nucleases and the nuclease–DNA complexes, respectively. It has been demonstrated that the developed force field parameters and atomic charges can consistently reproduce molecular geometries and conformations in the available X-ray crystal structures and can reasonably predict the interaction properties of the nucleases with DNA. The developed force field parameters in this work provide an extension of the AMBER force field for its application to computational modeling and simulations of the copper-based artificial nucleases associated with DNA.
Co-reporter:Yanyan Zhu;Zhanfen Chen;Zijian Guo
Journal of Molecular Modeling 2009 Volume 15( Issue 5) pp:
Publication Date(Web):2009 May
DOI:10.1007/s00894-008-0432-7
Theoretical studies on the coordination stabilities, spectra and DNA-binding trend for the series of metal-varied complexes, M(IDB)Cl2 (M = Mn, Fe, Co, Ni, Cu and Zn; IDB = N, N -bis(2-benzimidazolylmethyl) amine), have been carried out by using the DFT/B3LYP method and PCM model. The calculated coordination stabilities (S) for these complexes present a trend of S(Ni) > S(Co) > S(Fe) > S(Cu) > S(Zn) > S(Mn). It has been estimated from the molecular orbital energies of the complexes that the DNA-binding affinities (A) of the complexes are in the order of A(Zn) < A(Mn) < A(Fe) ≈ A(Co) < A(Ni) < A(Cu). The studied results indicate that the Cu, Ni and Co complexes with large coordination stabilities present the low virtual orbitals, consequently yielding to the favorable DNA-binding affinities. The spectral properties of excitation energies and oscillator strengths for M(IDB)Cl2 in the ultraviolet region were calculated by TD-DFT/B3LYP method.
Co-reporter:Qingxia Lu;Xichen Li;Guangju Chen
Journal of Molecular Modeling 2009 Volume 15( Issue 11) pp:1397-1405
Publication Date(Web):2009 November
DOI:10.1007/s00894-009-0505-2
The systematical investigations on the catalytic mechanisms of dismutation reactions for the superoxide dismutase (SOD) mimics of Cu(bpy)Br2 and its derivatives Cu(L1)Br2 and Cu(L2)Br2 (bpy=2,2’- dipyridyl, L1=5,5’- di[1- (triethylammonio)methyl]- 2,2’- dipyridyl cation and L2=5,5’- di [1- (tributylammonio)methyl]- 2,2’- dipyridyl cation) have been carried out by the DFT/UB3LYP method. The catalytic reaction for each of these compounds is confirmed to be a redox cycle consisting of two half-reactions. In the first half-reaction, a proton is transferred from hydroperoxide neutral radical (·OOH) to one nitrogen atom of pyridinic ring with Cu(II) being reduced to Cu(I) in the meantime. In the second half-reaction, the proton is transferred back to another hydroperoxide radical (·OOH) to form hydrogen peroxide molecule, oxidizing Cu(I) back to its initial state. Our results show that the first half-reaction for all reactions is the rate-controlling step with the forward barrier values of 6.61, 4.84, 3.79 kcal·mol−1 for Cu(bpy)Br2, Cu(L1)Br2, and Cu(L2)Br2, respectively. Consequently, the SOD-like activities of the three mimics are in the order of Cu(bpy)Br2 < Cu(L1)Br2 < Cu(L2)Br2. The effect factors on the SOD-like activity for the studied compounds have also been discussed.
Co-reporter:Yanyan Zhu, Yan Wang and Guangju Chen
The Journal of Physical Chemistry B 2009 Volume 113(Issue 3) pp:839-848
Publication Date(Web):December 29, 2008
DOI:10.1021/jp8091545
Molecular dynamics simulations for the ligand [Cu(BPA)]2+ (BPA = bis(2-pyridylmethyl)amine) nuclease bound to either the single-chain polyamide, ImPyImImPyβDp, or the antiparallel double-polyamide, (ImImImβDp)2, and associated with DNA were performed to predict the improvement of selective DNA cleavage ability of copper-based chemical nucleases. The results from the simulations indicate that either polyamide-bound [Cu(BPA)]2+ + OOH− (which is a necessary substrate in the redox mechanism of DNA cleavage) can locate in the minor groove of DNA in the parallel orientation similar to the X-ray structure. As a consequence of the polyamide + [Cu(BPA)]2+ + OOH− ligand binding to DNA, the active end oxygen atom of the OOH− substrate is held in close proximity to the known target C1′H or C4′H protons of the DNA. Upon examinations of six different ligands binding to DNA, the binding interaction of the entire ligand with DNA for each polyamide increases with the presence of [Cu(BPA)]2+ + OOH− ligand. The N−H groups of the linking regions from polyamide play an important role for the interaction by functioning as H-bond donors to N or O atoms of the nucleobase located on the floor of the minor groove of DNA. The investigation provides the feasible protocol to improve the selective DNA cleavage activity of chemical nucleases assisted by DNA recognition agents.
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