Biomedical subjects

John Z H Zhang

Publications and source records attributed to John Z H Zhang.

14 recordsLinked to original sources

PubMed2006

Nonadiabatic effects in the H+D2 reaction.

The state-to-state dynamics of the H+D2 reaction is studied by the reactant-product decoupling method using the double many-body expansion potential energy surface. Two approaches are compared: one uses only the lowest adiabatic sheet while the other employs both coupled diabatic sheets. Rotational distributions for the reaction H+D2 (upsilon = 0, j = 0)-->HD(upsilon' = 3, j')+D are obtained at eight different collision energies between 1.49 and 1.85 eV; no significant difference are found between the two approaches. Initial state-selected total reaction probabilities and integral cross sections are also given for energies ranging from 0.25 up to 2.0 eV with extremely small differences being observed between the two sets of results, thus showing that the nonadiabatic effects in the title reaction are negligible at least for small energies below 2.0 eV.

Journal Article↗

PubMed2006

Dissociation of heme from gaseous myoglobin ions studied by infrared multiphoton dissociation spectroscopy and Fourier-transform ion cyclotron resonance mass spectrometry.

Detachment of heme prosthetic groups from gaseous myoglobin ions has been studied by collision-induced dissociation and infrared multiphoton dissociation in combination with Fourier-transform ion cyclotron resonance mass spectrometry. Multiply charged holomyoglobin ions (hMbn+) were generated by electrospray ionization and transferred to an ion cyclotron resonance cell, where the ions of interest were isolated and fragmented by either collision with Ar atoms or irradiation with 3 mum photons, producing apomyoglobin ions (aMbn+). Both charged heme loss (with [Fe(III)-heme]+ and aMb(n-1)+ as the products) and neutral heme loss (with [Fe(II)-heme] and aMbn+ as the products) were detected concurrently for hMbn+ produced from a myoglobin solution pretreated with reducing reagents. By reference to Ea = 0.9 eV determined by blackbody infrared radiative dissociation for charged heme loss of ferric hMbn+, an activation energy of 1.1 eV was deduced for neutral heme loss of ferrous hMbn+ with n = 9 and 10.

Apoproteins↗

PubMed2006

A new quantum method for electrostatic solvation energy of protein.

A new method that incorporates the conductorlike polarizable continuum model (CPCM) with the recently developed molecular fractionation with conjugate caps (MFCC) approach is developed for ab initio calculation of electrostatic solvation energy of protein. The application of the MFCC method makes it practical to apply CPCM to calculate electrostatic solvation energy of protein or other macromolecules in solution. In this MFCC-CPCM method, calculation of protein solvation is divided into calculations of individual solvation energies of fragments (residues) embedded in a common cavity defined with respect to the entire protein. Besides computational efficiency, the current approach also provides additional information about contribution to protein solvation from specific fragments. Numerical studies are carried out to calculate solvation energies for a variety of peptides including alpha helices and beta sheets. Excellent agreement between the MFCC-CPCM result and those from the standard full system CPCM calculation is obtained. Finally, the MFCC-CPCM calculation is applied to several real proteins and the results are compared to classical molecular mechanics Poisson-Boltzmann (MM/PB) and quantum Divid-and-Conque Poisson-Boltzmann (D&C-PB) calculations. Large wave function distortion energy (solute polarization energy) is obtained from the quantum calculation which is missing in the classical calculation. The present study demonstrates that the MFCC-CPCM method is readily applicable to studying solvation of proteins.

Computer Simulation↗

PubMed2006

Energy and electron transfer in beta-alkynyl-linked porphyrin-[60]fullerene dyads.

Three porphyrin-fullerene dyads, in which a diyne bridge links C(60) with a beta-position on a tetraarylporphyrin, have been synthesized. The free-base dyad was prepared, as well as the corresponding Zn(II) and Ni(II) materials. These represent the first examples of a new class of conjugatively linked electron donor-acceptor systems in which pi-conjugation extends from the porphyrin ring system directly to the fullerene surface. The processes that occur following photoexcitation of these dyads were examined using fluorescence and transient absorption techniques on the femtosecond, picosecond, and nanosecond time scales. In sharp contrast to the photodynamics associated with singlet excited-state decay of reference tetraphenylporphyrins (ZnTPP, NiTPP, and H(2)TPP), the diyne-linked dyads undergo ultrafast (<10 ps) singlet excited-state deactivation in toluene, tetrahydrofuran (THF), and benzonitrile (PhCN). Transient absorption techniques with the ZnP-C(60) dyad clearly show that in toluene intramolecular energy transfer (EnT) to ultimately generate C(60) triplet excited states is the dominant singlet decay mechanism, while intramolecular electron transfer (ET) dominates in THF and PhCN to give the ZnP(*+)/C(60)(*-) charge-separated radical ion pair (CSRP). Electrochemical studies indicate that there is no significant charge transfer in the ground states of these systems. The lifetime of ZnP(*+)/C(60)(*-) in PhCN was approximately 40 ps, determined by two different types of transient absorption measurement in two different laboratories. Thus, in this system, the ratio of the rates for charge separation (k(CS)) to rates for charge recombination (k(CR)), k(CS)/k(CR), is quite small, approximately 7. The fact that charge separation (CS) rates increase with increasing solvent polarity is consistent with this process occurring in the normal region of the Marcus curve, while the slower charge recombination (CR) rates in less polar solvents indicate that the CR process occurs in the Marcus inverted region. While photoinduced ET occurs on a similar time scale in a related dyad 15 in which a diethynyl bridge connects C(60) to the para position of a meso phenyl moiety of a tetrarylporphyrin, CR occurs much more slowly; i.e., k(CS)/k(CR) approximately equal to 7400. Thus, the position at which the conjugative linker is attached to the porphyrin moiety has a dramatic influence on k(CR) but not on k(CS). On the basis of electron density calculations, we tentatively conclude that unfavorable orbital symmetries inhibit charge recombination in 15 vis a vis the beta-linked dyads.

Alkynes↗

PubMed2006

The generalized molecular fractionation with conjugate caps/molecular mechanics method for direct calculation of protein energy.

A generalized molecular fractionation with conjugate caps/molecular mechanics (GMFCC/MM) scheme is developed for efficient linear-scaling quantum mechanical calculation of protein energy. In this GMFCC/MM scheme, the interaction energy between neighboring residues as well as between non-neighboring residues that are spatially in close contact are computed by quantum mechanics while the rest of the interaction energy is computed by molecular mechanics. Numerical studies are carried out to calculate torsional energies of six polypeptides using the GMFCC/MM approach and the energies are shown to be in general good agreement with the full system quantum calculation. Among those we tested is a polypeptide containing 396 atoms whose energies are computed at the MP26-31G* level. Our study shows that using GMFCC/MM, it is possible to perform high level ab initio calculation such as MP2 for applications such as structural optimization of protein complex and molecular dynamics simulation.

Algorithms↗

PubMed2006

Nonadiabatic reactant-product decoupling calculation for the F(2P(1/2)) + H2 reaction.

In this paper we present a theoretical study using time-dependent nonadiabatic reactant-product decoupling method for the state-to-state reactive scattering calculation of F((2)P(1/2))+H(2) (nu=j=0) reaction on the Alexander-Stark-Werner potential energy surface. In this nonadiabatic state-to-state calculation, the full wave function is partitioned into reactant component and a sum of all product components. The reactant and product components of the wave function are solved independently. For the excited state reaction, the state-to-state reaction probabilities for J=0.5 are calculated. Comparing the state-to-state reaction probabilities, it is found that the vibrational population of the HF product is dominated by vibrational levels nu=2 and 3. The rotation specific reaction probabilities of HF product in j=1 and 2 are larger than those in other rotational levels. As the rotation quantum number j increases, the positions of the peak in the rotational reaction probability of HF product in nu=3 shift to higher collision energy.

Journal Article↗

PubMed2005

Quantum computational analysis for drug resistance of HIV-1 reverse transcriptase to nevirapine through point mutations.

Quantum chemical calculation has been carried out to analyze binding interactions of nevirapine to HIV-1 reverse transcriptase (RT) and single point mutants Lys103 --> Asn (K103N) and Tyr181--> Cys (Y181C). In this study, the entire system of HIV-1 RT/nevirapine complex with over 15,000 atoms is explicitly treated by using a recently developed MFCC (molecular fractionation with conjugate caps) approach. Quantum calculation of protein-drug interaction energy is performed at Hartree-Fock and DFT levels. The RT-nevirapine interaction energies are computed at fixed geometries given by the crystal structures of the HIV-1 RT/nevirapine complexes from protein data bank (PDB). The present calculation provides a quantum mechanical interaction spectrum that explicitly shows interaction energies between nevirapine and individual amino-acid fragments of RT. Detailed interactions that are responsible for drug resistance of two major RT mutations are elucidated based on computational analysis in relation to the crystal structures of binding complexes. The present result provides a qualitative molecular understanding of HIV-1 RT drug resistance to nevirapine and gives useful guidance in designing improved inhibitors with better resistance to RT mutation.

Anti-HIV Agents↗

PubMed2005

An efficient approach for ab initio energy calculation of biopolymers.

We present a new method for efficient total-energy calculation of biopolymers using the density-matrix (DM) scheme based on the molecular fractionation with conjugate caps (MFCC) approach. In this MFCC-DM method, a biopolymer such as a protein is partitioned into properly capped fragments whose density matrices are calculated by conventional ab initio methods which are then assembled to construct the full system density matrix. The assembled full density matrix is then employed to calculate the total energy and dipole moment of the protein using Hartree-Fock or density-functional theory methods. Using this MFCC-DM method, the self-consistent-field procedure for solving the full Hamiltonian problem is avoided and an efficient approach for ab initio energy calculation of biopolymers is achieved. Two implementations of the approach are presented in this paper. Systematic numerical studies are carried out on a series of extended polyglycines CH3CO-(GLY)n-NHCH3(n = 3-25) and excellent results are obtained.

Biopolymers↗

PubMed2005

A new method for direct calculation of total energy of protein.

A new scheme is developed for efficient quantum mechanical calculation of total energy of protein based on a recently developed MFCC (molecular fractionation with conjugate caps) approach. In this scheme, the linear-scaling MFCC method is first applied to calculate total electron density of protein. The computed electron density is then employed for direct numerical integration in density functional theory (DFT) to yield total energy of protein, with the kinetic energy obtained by a proposed ansatz. Numerical studies are carried out to calculate torsional energies of two polypeptides using this approach and the energies are shown to be in good agreement with the corresponding full system DFT calculation.

Models, Chemical↗

PubMed2004

Theoretical method for full ab initio calculation of DNA/RNA-ligand interaction energy.

In this paper, we further develop the molecular fractionation with conjugate caps (MFCC) scheme for quantum mechanical computation of DNA-ligand interaction energy. We study three oligonuclear acid interaction systems: dinucleotide dCG/water, trinucleotide dCGT/water, and a Watson-Crick paired DNA segment, dCGT/dGCA. Using the basic MFCC approach, the nucleotide chains are cut at each phosphate group and a pair of conjugate caps (concaps) are inserted. Five cap molecules have been tested among which the dimethyl phosphate anion is proposed to be the standard concap for application. For each system, one-dimensional interaction potential curves are computed using the MFCC method and the calculated interaction energies are found to be in excellent agreement with corresponding results obtained from the full system ab initio calculations. The current study extends the application of the MFCC method to ab initio calculations for DNA- or RNA-ligand interaction energies.

Algorithms↗

PubMed2004

Quantum scattering calculation of the O(1D)+HBr reaction.

Three-dimensional time-dependent quantum wave packet calculation for the O((1)D)+HBr reaction has been carried out using an accurate ab initio global potential energy surface [K. A. Peterson, J. Chem. Phys. 113, 4598 (2000)]. The calculations show that the initial state-selected reaction probabilities are dominated by resonance structures, and the lifetime of the resonance is generally in the subpicosecond time scale. The energy dependence of the reaction cross section is computed, which manifests still resonance structures, and is a decreasing function of the translational energy. The thermal rate constants are also computed, which are nearly independent on the temperature. The calculation results are discussed and compared to similar reaction with deep well.

Journal Article↗

PubMed2004

The investigation of spin-orbit effect for the F((2)P)+HD reaction.

In this paper, we employ the time-dependent quantum wave packet method to study the reaction of F((2)P(3/2), (2)P(1/2)) with HD on the Alexander-Stark-Werner potential energy surface. The reaction probabilities and total integral cross sections of the spin-orbit ground and excited states for the two possible products of the system are calculated. Because the reaction channel of the excited spin-orbit state is closed at the resonance energy, the resonance feature does not appear in the reaction probabilities and cross section for the F((2)P(1/2))+HD(v=j=0)-->HF+D reaction, in contrast with that found for the ground spin--orbit state. We also compare the average cross sections of the two possible products with the experimental measurement. The resonance peak in the present average cross section for the HF+D product is slightly larger than the experimental result, but much smaller than that of the single-state calculations on the potential energy surface of Stark and Werner. It seems that the spin--orbit coupling would play a relatively important role in this reaction. Moreover, the isotope effects of the ground and excited spin--orbit states and the reactivity of the two product channels from the excited spin--orbit state are presented.

Journal Article↗

PubMed2004

Quantum mechanical map for protein-ligand binding with application to beta-trypsin/benzamidine complex.

We report full ab initio Hartree-Fock calculation to compute quantum mechanical interaction energies for beta-trypsin/benzamidine binding complex. In this study, the full quantum mechanical ab initio energy calculation for the entire protein complex with 3238 atoms is made possible by using a recently developed MFCC (molecular fractionation with conjugate caps) approach in which the protein molecule is decomposed into amino acid-based fragments that are properly capped. The present MFCC ab initio calculation enables us to obtain an "interaction spectrum" that provides detailed quantitative information on protein-ligand binding at the amino acid levels. These detailed information on individual residue-ligand interaction gives a quantitative molecular insight into our understanding of protein-ligand binding and provides a guidance to rational design of potential inhibitors of protein targets.

Aspartic Acid↗

PubMed2004

Fully quantum mechanical energy optimization for protein-ligand structure.

We present a quantum mechanical approach to study protein-ligand binding structure with application to a Adipocyte lipid-binding protein complexed with Propanoic Acid. The present approach employs a recently develop molecular fractionation with a conjugate caps (MFCC) method to compute protein-ligand interaction energy and performs energy optimization using the quasi-Newton method. The MFCC method enables us to compute fully quantum mechanical ab initio protein-ligand interaction energy and its gradients that are used in energy minimization. This quantum optimization approach is applied to study the Adipocyte lipid-binding protein complexed with Propanoic Acid system, a complex system consisting of a 2057-atom protein and a 10-atom ligand. The MFCC calculation is carried out at the Hartree-Fock level with a 3-21G basis set. The quantum optimized structure of this complex is in good agreement with the experimental crystal structure. The quantum energy calculation is implemented in a parallel program that dramatically speeds up the MFCC calculation for the protein-ligand system. Similarly good agreement between MFCC optimized structure and the experimental structure is also obtained for the streptavidin-biotin complex. Due to heavy computational cost, the quantum energy minimization is carried out in a six-dimensional space that corresponds to the rigid-body protein-ligand interaction.

Carrier Proteins↗