Co-reporter:Qing Wang, Yu Tian, Guangju Chen, Jingxiang Zhao
Applied Surface Science 2017 Volume 397(Volume 397) pp:
Publication Date(Web):1 March 2017
DOI:10.1016/j.apsusc.2016.11.048
•We studied the deposition of several Pt-based alloy NPs on N-doped defective graphene.•The N-doped graphene can provide anchoring site for Pt-based NPs.•The electronic properties of Pt-based NPs have been greatly modified.•The catalytic properties of Pt-based NPs can be enhanced.Enhancing the catalytic activity and decreasing the usage of Pt catalysts has been a major target in widening their applications for developing proton-exchange membrane fuel cells. In this work, the adsorption energetics, structural features, and electronic properties of several MPt12 (M = Fe, Co, Ni, Cu, and Pd) nanoparticles (NPs) deposited on N-doped defective graphene were systemically explored by means of comprehensive density functional theory (DFT) computations. The computations revealed that the defective N-doped graphene substrate can provide anchoring site for these Pt-based alloying NPs due to their strong hybridization with the sp2 dangling bonds at the defect sites of substrate. Especially, these deposited MPt12 NPs exhibit reduced magnetic moment and their average d-band centers are shifted away from the Fermi level, as compared with the freestanding NPs, leading to the reduction of the adsorption energies of the O species. Thus, the defective N-doped graphene substrate not only enhances the stability of the deposited MPt12 NPs, but also endows them higher catalytic performance for the oxygen reduction reaction.
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;Yan 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:Qing-Jun Zang, Guang-Ju Chen, Wen-Cai Lu
Chemical Physics Letters 2012 Volume 552() pp:69-72
Publication Date(Web):12 November 2012
DOI:10.1016/j.cplett.2012.09.023
Snn (n = 34–44) clusters were studied using a combined method of the genetic algorithm/tight-binding search and the DFT–PBEPBE calculations. Snn (n = 34–44) clusters are shown to favor an assembly motif composed of small stable Sn9 and Sn10 subunits which are connected by cohesive linkages of smaller clusters (Sn1–5). Snn (n = 34–44) clusters were found to transform from a prolate pattern for Sn34,35 to a ‘Y’ pattern for Sn36–39 to a plate motif for Sn40–44. Obvious structural transitions would easily occur at the cross points of binding energy curves when isomers become competitive.Graphical abstractStructural transition from prolate to ‘Y’ to plate motif for Sn34–44 clusters.Highlights► Snn (n = 34–44) transform from a prolate for Sn34,35 to a ‘Y’ type for Sn36–39 to a plate for Sn40–44. ► Structural transitions would easily occur at cross points of the binding energy curves. ► Snn (n = 34–44) favor an assembly motif composed of Sn9 and Sn10.
Co-reporter:Yaru Wang;Yanyan Zhu;Yan Wang;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;Yan Wang;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:Xichen Li, Rong-Zhen Liao, Wenchang Zhou and Guangju Chen
Physical Chemistry Chemical Physics 2010 vol. 12(Issue 16) pp:3961-3971
Publication Date(Web):28 Jan 2010
DOI:10.1039/B918402C
We describe theoretical insights into the mechanism of Hg–C bond protonolysis in methyl mercury coordinated by the tris(2-mercapto-1-tert-butylimidazolyl)hydroborato ligand, the structural and functional analogue of the organomercurial lyase MerB. Different cleavage pathways including both frontside and backside attack transition states were systematically studied by the hybrid density functional method B3LYP. Dependence of Hg–C bond activation on the primary sulfur coordination number of mercury was elaborated, and conceptual DFT indexes were suggested to be more appropriate than gross charge of atom sites in interpreting the dependence. Furthermore, absence of configurational inversion in MerB-catalyzed reactions was accounted for by examinations of the backside protonolysis pathways in the present system. Lastly, a rationalization was provided about the choice between different characteristics of transition states including both four-center and six-center ones.
Co-reporter:Yong Zhang;Hongwei Tan;Guangju Chen;Zongchao Jia
Journal of Molecular Recognition 2010 Volume 23( Issue 4) pp:360-368
Publication Date(Web):
DOI:10.1002/jmr.1002
Abstract
We have studied the conformational transition of the calmodulin binding domains (CBD) in several calmodulin-binding kinases, in which CBD changes from the disordered state to the ordered state when binding with calmodulin (CaM). Targeted molecular dynamics simulation was used to investigate the binding process of CaM and CBD of CaM-dependent kinase I (CaMKI–CBD). The results show that CaMKI–CBD began to form an α-helix and the interaction free energy between CaM and CaMKI–CBD increased once CaM fully encompassed CaMKI–CBD. Two series of CaM/CBD complex systems, including the complexes of CaM with the initially disordered and the final ordered CBD, were constructed to study the interaction using molecular dynamics simulations. Our analyses suggest that the VDW interaction plays a dominant role in CaM/CBD binding and is a key factor in the disorder–order transition of CBD. Additionally, the entropy effect is not in favor of the formation of the CaM/CBD complex, which is consistent with the experimental evidence. Based on the results, it appears that the CBD conformational change from a non-compact extended structure to compact α-helix is critical in gaining a favorable VDW interaction and interaction free energy. Copyright © 2009 John Wiley & Sons, Ltd.
Co-reporter:Hongwei Yue;Yanyan Zhu;Yan Wang;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;Yan Wang;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, 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.
Co-reporter:Qingxia Lu;Xichen Li;Yan Wang;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;Zhanfen Chen;Zijian Guo;Yan Wang
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:Xichen Li, Wenlan Liu, Kening Sun, Yan Wang, Hongwei Tan and Guangju Chen
Physical Chemistry Chemical Physics 2008 vol. 10(Issue 36) pp:5607-5615
Publication Date(Web):24 Jul 2008
DOI:10.1039/B804291H
This paper presents a theoretical study of the cooperative effect in sixteen linearly-arranged trimer systems consisting of N-methylformamide dimer and an extra amino acid residue. These trimer systems, NMF–NMF–AAR, in short, have been systematically investigated by full optimization at B3LYP/cc-pVTZ level and subsequent electronic energy calculations at PBE1PBE/cc-pVTZ, HF/cc-pVTZ and MP2/cc-pVTZ, respectively. Obvious spatial transformation due to energetic factors has been found in almost all the trimers. Systematic analysis in weak interaction energy components has shown that: (1) in these trimer systems, the bonding structure and the cooperative effect combine to determine the stability of both HB1 and HB2. For HB2, the structure of the constituent amino acid residue also plays a crucial role by interfering with the neighboring moieties; (2) the large contribution of the cooperative effect to the overall hydrogen bonding energy has claimed the importance of cooperativity in our systems; (3) the non-hydrogen bonding weak interaction components are found to be non-negligible in these trimer systems; (4) moreover, the cooperative effect between these non-hydrogen bonding components is always found to be positive. The good performances of PBE1PBE and PM6 have been established by comparisons between these methods.
Co-reporter:Yong Zhang;Hongwei Tan;Zongchao Jia;Guangju Chen
Journal of Molecular Recognition 2008 Volume 21( Issue 4) pp:267-274
Publication Date(Web):
DOI:10.1002/jmr.895
Abstract
Calmodulin (CaM) can bind to numerous proteins in several interaction modes. Recently a new mode of interaction was discovered, in which two CaM molecules form an X-shaped dimer and two binding sites to trap the CaM-binding domain (CBD) of calcineurin subunit A. However, the X-shaped CaM dimer alone without ligand has not been observed. We performed molecular dynamics (MD) simulations and used MM_PBSA approach to investigate the properties of this new binding mode using ligand-bound and -free dimer systems. MD trajectories show that two peptides of CBD play a critical role in stabilizing the X-shaped conformation of the CaM dimer which would otherwise be unstable, leading to dimer disassembly in the absence of the ligands. Furthermore, we have analyzed the interaction free energy of the complex by MM-PBSA method and provide further evidence to demonstrate that the CBD peptide ligands are responsible for the stabilization of the dimer. Comparing this new binding mode with the classical one represented by CaM in complex with smooth muscle myosin light chain kinase, we conclude that this new binding mode isinduced by the CBD of calcineurin subunit A. Our results explain the fact that the X-shaped CaM dimer structure has never been observed in the absence of ligands. Copyright © 2008 John Wiley & Sons, Ltd.
Co-reporter:Lan Hao;XiChen Li;HongWei Tan;GuangJu Chen
Science China Chemistry 2008 Volume 51( Issue 4) pp:359-366
Publication Date(Web):2008 April
DOI:10.1007/s11426-007-0112-y
Platinum-based antitumour drug ZD0473 was designed to reduce the cisplatin resistance to the tumor cells. In this paper, the mixed method of molecular mechanics and quantum chemistry, HF/lanl2dz// MM/uff and B3LYP/lanl2dz//6-31G*, are used to investigate the differences between four types of GG, 3′AG5′, 3′GA5′, and AA complexes, which are formed from four discrete DNA fragments recognized by ZD0473 and cisplatin. The results show that the binding interaction of both ZD0473 and cisplatin drugs with the GG base pair is much stronger than with other base pairs, namely the recognition capability of such drugs to the GG base pair is more considerable. Moreover, the interaction of four complexes of ZD0473 with DNA fragments is stronger than that of cisplatin with corresponding DNA fragments, which indicates the stronger binding capability of ZD0473 with DNA fragments and high antitumour activity of ZD0473. The main reason for easier forming of 3′GA5′ complex than the 3′AG5′ one is that the drug molecule prefers to bind with a single G base to form a monoligand compound firstly; then the configuration transformation from such monoligand compound to the bi-ligand one is limited.
Co-reporter:YanXia Zhou;HongWei Tan;ZuoYin Yang;ZongChao Jia
Science China Chemistry 2007 Volume 50( Issue 2) pp:266-271
Publication Date(Web):2007 April
DOI:10.1007/s11426-007-0027-7
The insect spruce budworm (Choristoneura fumiferana) produces antifreeze protein (AFP) to assist in the protection of the over-wintering larval stage and contains multiple isoforms. Structures for two isoforms, known as CfAFP-501 and CfAFP-337, show that both possess similar left-handed β-helical structure, although thermal hysteresis activity of the longer isoform CfAFP-501 is three times that of CfAFP-337. The markedly enhanced activity of CfAFP-501 is not proportional to, and cannot be simply accounted for, by the increased ice-binding site resulting from the two extra coils in CfAFP-501. In order to investigate the molecular basis for the activity difference and gain better understanding of AFPs in general, we have employed several different computational methods to systematically study the structural properties and ice interactions of the AFPs and their deletion models. In the context of intact AFPs, a majority of the coils in CfAFP-501 has better ice interaction and causes stronger ice lattice disruption than CfAFP-337, strongly suggesting a cooperative or synergistic effect among β-helical coils. The synergistic effect would play a critical role and make significant contributions to the antifreeze activity β-helical antifreeze proteins. This is the first time that synergistic effect and its implication for antifreeze activity are reported for β-helical antifreeze proteins.
Co-reporter:Kai Liu;Yan Wang;Hongwei Tan;Guangju Chen;Zhenhe Tong
Frontiers in Biology 2007 Volume 2( Issue 2) pp:180-183
Publication Date(Web):2007 April
DOI:10.1007/s11515-007-0025-3
Based on the computational simulation with the vacuum environment for the fish-type-II antifreeze proteinice-solvent (water) system, the multi-complex system of the antifreeze protein-ice-water has been constructed and calculated. We have studied the interaction of such proteinice system with water solvent through the dynamics simulation with 350 ps. By employing the Molecular Dynamics simulation and semi-empirical method calculation, we have further investigated the interface properties of the antifreeze protein and ice crystal combined system. Consequently, a water solvent affects significantly the properties of this combined system.
Co-reporter:Wenwen Qu, Hongwei Tan, Guangju Chen and Ruozhuang Liu
Physical Chemistry Chemical Physics 2003 vol. 5(Issue 11) pp:2327-2332
Publication Date(Web):01 May 2003
DOI:10.1039/B300549F
Synthetic organic functional nanomaterials have been the subject of intense study lately due to their potential use in many fields. As a result, theoretical studies of such materials have also received extensive attention. In this paper, seven models of a novel photo-switchable self-organized peptide system were optimized using the semi-empirical molecular orbital method AM1, and single point calculations of three of them were investigated by means of the density functional B3LYP/3-21G* method. The geometries, energetics and frontier orbital interactions of these photo-switchable peptide subsystems were calculated and analyzed. Our results provide insight into the formation, self-assembly and photo-isomerization of the system. Weak interactions between two polypeptide rings, especially hydrogen-bonding interactions, are crucial for stabilizing the conformation and self-assembly. Remarkably, oligomers of the E form show almost no cooperative effect, strongly supporting the notion that it is possible to break the intermolecular hydrogen bonds to enable E→Z isomerization reactions. Moreover, the polypeptide rings strengthen the conjugation effect on azobenzene subunits and lead to a reduction in the frontier molecular orbital energy differences. The self-assembling process of the E form also reinforces frontier orbital interactions and favors E→Z isomerization.
Co-reporter:Yong Zhang, Hongwei Tan, Yanyan Lu, Zongchao Jia, Guangju Chen
FEBS Letters (16 April 2008) Volume 582(Issue 9) pp:1355-1361
Publication Date(Web):16 April 2008
DOI:10.1016/j.febslet.2008.03.010
We used steered molecular dynamics (SMD) to simulate the process of Ca2+ dissociation from the EF-hand motifs of the C-terminal lobe of calmodulin. Based on an analysis of the pulling forces, the dissociation sequences and the structural changes, we show that the Ca2+-coordinating residues lose their binding to Ca2+ in a stepwise fashion. The two Ca2+ ions dissociate from the two EF-hands simultaneously, with two distinct groups among the five Ca2+-coordinating residues affecting the EF-hand conformational changes differently. These results provide new insights into the effects of Ca2+ on calmodulin conformation, from which a novel sequential mechanism of Ca2+-calmodulin dissociation is proposed.
Co-reporter:Xichen Li, Wenlan Liu, Kening Sun, Yan Wang, Hongwei Tan and Guangju Chen
Physical Chemistry Chemical Physics 2008 - vol. 10(Issue 36) pp:NaN5615-5615
Publication Date(Web):2008/07/24
DOI:10.1039/B804291H
This paper presents a theoretical study of the cooperative effect in sixteen linearly-arranged trimer systems consisting of N-methylformamide dimer and an extra amino acid residue. These trimer systems, NMF–NMF–AAR, in short, have been systematically investigated by full optimization at B3LYP/cc-pVTZ level and subsequent electronic energy calculations at PBE1PBE/cc-pVTZ, HF/cc-pVTZ and MP2/cc-pVTZ, respectively. Obvious spatial transformation due to energetic factors has been found in almost all the trimers. Systematic analysis in weak interaction energy components has shown that: (1) in these trimer systems, the bonding structure and the cooperative effect combine to determine the stability of both HB1 and HB2. For HB2, the structure of the constituent amino acid residue also plays a crucial role by interfering with the neighboring moieties; (2) the large contribution of the cooperative effect to the overall hydrogen bonding energy has claimed the importance of cooperativity in our systems; (3) the non-hydrogen bonding weak interaction components are found to be non-negligible in these trimer systems; (4) moreover, the cooperative effect between these non-hydrogen bonding components is always found to be positive. The good performances of PBE1PBE and PM6 have been established by comparisons between these methods.
Co-reporter:Xichen Li, Rong-Zhen Liao, Wenchang Zhou and Guangju Chen
Physical Chemistry Chemical Physics 2010 - vol. 12(Issue 16) pp:NaN3971-3971
Publication Date(Web):2010/01/28
DOI:10.1039/B918402C
We describe theoretical insights into the mechanism of Hg–C bond protonolysis in methyl mercury coordinated by the tris(2-mercapto-1-tert-butylimidazolyl)hydroborato ligand, the structural and functional analogue of the organomercurial lyase MerB. Different cleavage pathways including both frontside and backside attack transition states were systematically studied by the hybrid density functional method B3LYP. Dependence of Hg–C bond activation on the primary sulfur coordination number of mercury was elaborated, and conceptual DFT indexes were suggested to be more appropriate than gross charge of atom sites in interpreting the dependence. Furthermore, absence of configurational inversion in MerB-catalyzed reactions was accounted for by examinations of the backside protonolysis pathways in the present system. Lastly, a rationalization was provided about the choice between different characteristics of transition states including both four-center and six-center ones.
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