Molecular mechanics and dynamics of biomolecules using a solvent continuum model

An easy implementation of molecular mechanics and molecular dynamics simulation using a continuum solvent model is presented that is particularly suitable for biomolecular simulations. The computation of solvation forces is made using the linear Poisson-Boltzmann equation (polar contribution) and the solvent-accessible surface area approach (nonpolar contribution). The feasibility of the methodology is demonstrated on a small protein and a small DNA hairpin. Although the parameters employed in this model must be refined to gain reliability, the performance of the method, with a standard choice of parameters, is comparable with results obtained by explicit water simulations. Copyright 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1830-1842, 2001     

A minimal model for stabilization of biomolecules by hydrocarbon cross-linking

Programmed cell death regulating protein motifs play an essential role in the development of an organism, its immune response, and disease-related cellular mechanisms. Among those motifs the BH3 domain of the BCL-2 family is found to be of crucial importance. Recent experiments showed how the isolated, otherwise unstructured BH3 peptide can be modified by a hydrocarbon linkage to regain function. We parametrized a reduced, dynamic model for the stability effects of such covalent cross-linking and confirmed that the model reproduces the reinforcement of the structural stability of the BH3 motif by cross-linking. We show that an analytically solvable model for thermostability around the native state is not capable of reproducing the stabilization effect. This points to the crucial importance of the peptide dynamics and the fluctuations neglected in the analytic model for the cross-linking system to function properly. This conclusion is supported by a thorough analysis of a simulated Go model. The resulting model is suitable for rational design of generic cross-linking systems in silicio.     

Atomistic kinetic model for population shift and allostery in biomolecules

Allosteric signaling in biomolecules is a key mechanism for a myriad of cellular processes. We present a general yet compact model for protein allostery at atomic detail to quantitatively explain and predict structural-dynamics properties of allosteric signal propagation. The master equation-based approach for allostery by population shift (MAPS) is introduced that derives the time scales, amplitudes, and pathways of signal transmission in peptides and proteins from dihedral angle dynamics observed in extended molecular dynamics simulations. The MAPS approach is first applied to the alanine-pentapeptide, and the results are tested against an explicit simulation in the presence of local conformational constraints, confirming the validity and accuracy of the model. We then apply the approach to a larger Markovian system based on a millisecond all-atom protein molecular dynamics trajectory of BPTI (Shaw et al. Science 2010, 330, 341-346). We use MAPS to illustrate in silico the propagation of a local perturbation over medium- to long-range distances across a disulfide bridge linking loops L1 and L2, which constitute the binding interface of BPTI.     

Redox strategy for reversible attachment of biomolecules using bifunctional linkers

Soft attachment of streptavidin to β-cyclodextrin-modified pegylated SAMs was efficiently performed in a reversible and repetitive way via orthogonal bifunctional linkers involving streptavidin-biotin recognition and redox-driven multivalent host-guest (β-cyclodextrin-ferrocene) interactions.     

On expectation value calculations of one-electron properties using the coupled cluster wave functions

The ability of various approximate coupled cluster (CC) methods to provide accurate first-order one-electron properties calculated as expectation values is theoretically analysed and computationally examined for BH and CO. For actual calculations the infinite number of terms of the expectation value expansion (O=¦exp (T ⁺)O exp (T)¦_c) was truncated so that T ₁ T ₂, T ₃, and (1/2) T ₂T₂ clusters were retained on both sides of O. The role of individual clusters is carefully discussed. Inclusion of T ₁, is unavoidable, but if triples are essential in the energy evaluation, they may play an even more important role in the property expansion, as shown in the case of CO. It is shown that the CC wave function, which is exact to second order, effectively satisfies the Hellmann-Feynman theorem.     

Massive cluster impact mass spectrometry: a new desorption method for the analysis of large biomolecules.

A new ion desorption method is described that utilizes a primary beam of massive, multiply charged cluster ions to generate secondary ions of peptides in a glycerol matrix. The massive cluster ion beam is generated via electrohydrodynamic emission using a 1.5 M solution of ammonium acetate in 30% aqueous glycerol. Negative ion spectra of peptides obtained using this technique show greatly decreased relative intensities for fragment ions and 'chemical noise' background when compared to spectra obtained using a xenon atom primary beam. The near absence of fragments derived from radiation damage to the sample solution is attributed to the impact of primary particles with energies less than 1 eV/nucleon.     

Aqueous chromatographic system for separation of biomolecules using thermoresponsive polymer modified stationary phase

We have investigated a new method for HPLC using packing materials modified with a functional polymer, such as thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm). PNIPAAm-modified silica exhibits temperature-controlled hydrophilic-hydrophobic surface property changes in aqueous systems. Temperature-responsive chromatography is performed with an aqueous mobile phase without using an organic solvent. We designed ternary copolymers of NIPAAm introduced 2-(dimethyl-amino) ethyl methacrylate (DMAEMA) as a cationic monomer and butyl methacrylate (BMA) as a hydrophobic monomer. A cationic thermoresponsive hydrogel grafted surface would produce an alterable stationary phase with both thermally regulated hydrophobicity and charge density for separation of bioactive compounds. In this study, we achieved successful separation of lysozyme without the loss of bioactivity by temperature-responsive chromatography. The electrostatic and hydrophobic interactions could be modulated simultaneously with the temperature in an aqueous mobile phase, thus the separation system would have potential applications in the separation of biomolecules.     

Gas phase metal cluster model systems for heterogeneous catalysis

Since the advent of intense cluster sources, physical and chemical properties of isolated metal clusters are an active field of research. In particular, gas phase metal clusters represent ideal model systems to gain molecular level insight into the energetics and kinetics of metal-mediated catalytic reactions. Here we summarize experimental reactivity studies as well as investigations of thermal catalytic reaction cycles on small gas phase metal clusters, mostly in relation to the surprising catalytic activity of nanoscale gold particles. A particular emphasis is put on the importance of conceptual insights gained through the study of gas phase model systems. Based on these concepts future perspectives are formulated in terms of variation and optimization of catalytic materials e.g. by utilization of bimetals and metal oxides. Furthermore, the future potential of bio-inspired catalytic material systems are highlighted and technical developments are discussed.     

SCF-α Scattered wave model cluster calculations for the adsorption systems CO/Ni and N2/Ni

SCF-α-SW calculations have been performed on model clusters which can be taken as representations of chemisorbed CO and N₂ on Ni(100). As a check of the influence of the cluster size, NiCO/NiN₂ and Ni₉N₂ clusters have been studied as well as the isolated molecules CO and N₂ . In order to recognize and eliminate errors due to the differing muffintin geometries, other reference molecular clusters (CO/N₂ in an enlarge outer sphere, and on 9 empty spheres corresponding in size to Ni₉) have also been calculated. The discussion of results is based on (Xα ground state and transition state) energy shifts and on charge distributions. The main conclusions reached about the surface bond in the two cases (dative 5 σ bond and π backbond for CO; for N₂ main dative bond through 4σ with a smaller 5σ contribution, and a weaker π backbond than for CO) agree with those reached by other methods. Additional information (e.g σ backbond contribution for the large clusters; a strong localization of the adsorbate bond for N₂, but noticeable delocalization for CO) is derived.     

Continuum transport model of Ogston sieving in patterned nanofilter arrays for separation of rod-like biomolecules

This article proposes a simple computational transport model of rod-like short dsDNA molecules through a microfabricated nanofilter array. Using a nanochannel consisting of alternate deep wells and shallow slits, it is demonstrated that the complex partitioning of rod-like DNA molecules of different sizes over the nanofilter array can be well described by continuum transport theory with the orientational entropy and anisotropic transport parameters properly quantified. In this model, orientational entropy of the rod-like DNA is calculated from the equilibrium distribution of rigid cylindrical rod near the solid wall. The flux caused by entropic differences is derived from the interaction between the DNA rods and the solid channel wall during rotational diffusion. In addition to its role as an entropic barrier, the confinement of the DNA in the shallow channels also induces large changes in the effective electrophoretic mobility for longer molecules in the presence of EOF. In addition to the partitioning/selectivity of DNA molecules by the nanofilter, this model can also be used to estimate the dispersion of separated peaks. It allows for fast optimization of nanofilter separation devices, without the need of stochastic modeling techniques that are usually required.     

The Cotton-Mouton effect of neon and argon: a benchmark study using highly correlated coupled cluster wave functions

The Cotton-Mouton effect (magnetic field induced linear birefringence) has been studied for neon and argon using state-of-the-art coupled cluster techniques. The coupled cluster singles, doubles and triples (CCSDT) approach has been used to obtain static benchmark results and the CC3 model with an approximate treatment of triple excitations to obtain frequency-dependent results. In the case of neon the effect of excitations beyond triples has also been estimated via coupled cluster calculations including quadruple excitations (CCSDTQ), pentuple excitations (CCSDTQP), etc. up to the full configuration-interaction level. The results obtained for the anisotropy of the hypermagnetizability Deltaeta(omega), the molecular property that determines the magnetic field induced birefringence of spherically symmetric systems, are Deltaeta=2.89 a.u. for neon and Deltaeta=24.7 a.u. for argon, with a negligible effect of frequency dispersion. For neon we could estimate an absolute error on Deltaeta of 0.1 a.u. The accuracy of these results surpasses that of recently reported experimental data.     

原子簇量子化学从头算的自洽晶体场模型

本文提出一种收敛的点电荷和Hartree-Fock表面势构成的自洽晶体场Madelung势用于原子簇量子化学从头计算。前者的计算类似于核吸引积分的单电子积分, 后者可以通过点群对称性操作从原子簇内的积分矩阵元得到。点电荷的大小和原子簇内对应的原子电荷相等, 其数目以晶体场势收敛为标准确定。介绍加速计算的程序技巧。该模型用于高温超导体YBa2Cu3O7的全电子从头计算并得到一些新结果。     

Multiple cluster model (MCM) for surface reaction systems

Multiple cluster model (MCM) for investigating surface reactions is formulated. In this model the reaction center, where electron correlation effects often play a key role, is described by an accurate high‐level approximation, and bulk effects such as the lattice distortion energy are evaluated using a simple low‐level approximation. Therefore, the MCM can properly simulate the potential energy hypersurface of the surface reaction system with a feasible computational cost. Since there exists no fixed atom in the MCM, we can rigorously characterize the stationary point (the minimum energy point or the transition state) on the potential energy hypersurface by vibrational frequency analysis. The MCM can be applied not only to surface systems, but also to various large systems. A detailed comparison of the MCM with the integrated molecular orbital+molecular mechanics (IMOMM), the integrated molecular orbital+molecular orbital (IMOMO), and ONIOM developed by Morokuma and co‐workers is also presented. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 71: 403–413, 1999