A multiple time step algorithm compatible with a large number of distance classes and an arbitrary distance dependence of the time step size for the fast evaluation of nonbonded interactions in molecular simulations

A new algorithm is introduced to perform the multiple time step integration of the equations of motion for a molecular system, based on the splitting of the nonbonded interactions into a series of distance classes. The interactions between particle pairs in successive classes are updated at a progressively decreasing frequency. Unlike previous multiple time-stepping schemes relying on distance classes, the present algorithm sorts interacting particle pairs by their next update times rather than by their update frequencies. For this reason, the proposed scheme is extremely flexible with respect to the number of classes that can be employed (up to hundred or more) and the distance dependence of the relative time step size (arbitrary integer function of the distance). It can also easily be adapted to classes defined based on a criterion other than the interparticle distance (e.g., interaction magnitude). Different variants of the algorithm are tested in terms of accuracy and efficiency for simulations of a pure water system (6167 molecules) under truncated-octahedral periodic boundary conditions, and compared to the twin-range method standardly used with GROMOS96 (short- and long-range cutoff distances of 0.8 and 1.4 nm, pair list and intermediate-range interactions updated every five steps). In particular, multiple time-stepping schemes with an accuracy comparable to that of the twin-range method can be designed, that permit to increase the effective (long-range) cutoff distance from 1.4 to 3.0 nm with a performance loss of only about a factor 2. This result is quite encouraging, considering the benefits of doubling the cutoff radius in the context of (bio-)molecular simulations.     

Efficient nonbonded interactions for molecular dynamics on a graphics processing unit

We describe an algorithm for computing nonbonded interactions with cutoffs on a graphics processing unit. We have incorporated it into OpenMM, a library for performing molecular simulations on high‐performance computer architectures. We benchmark it on a variety of systems including boxes of water molecules, proteins in explicit solvent, a lipid bilayer, and proteins with implicit solvent. The results demonstrate that its performance scales linearly with the number of atoms over a wide range of system sizes, while being significantly faster than other published algorithms. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010     

An adaptive treecode for computing nonbonded potential energy in classical molecular systems

A treecode algorithm is presented for rapid computation of the nonbonded potential energy in classical molecular systems. The algorithm treats a general form of pairwise particle interaction with the Coulomb and London dispersion potentials as special cases. The energy is computed as a sum of group–group interactions using a variant of Appel's recursive strategy. Several adaptive techniques are employed to reduce the execution time. These include an adaptive tree with nonuniform rectangular cells, variable order multipole approximation, and a run‐time choice between direct summation and multipole approximation for each group–group interaction. The multipole approximation is derived by Taylor expansion in Cartesian coordinates, and the necessary coefficients are computed using a recurrence relation. An error bound is derived and used to select the order of approximation. Test results are presented for a variety of systems. © 2000 John Wiley & Sons, Inc. J Comput Chem 22: 184–195, 2001     

Development of a parallel molecular dynamics code on SIMD computers: Algorithm for use of pair list criterion

In recent years several implementations of molecular dynamics (MD) codes have been reported on multiple instruction multiple data (MIMD) machines. However, very few implementations of MD codes on single instruction multiple data (SIMD) machines have been reported. The difficulty in using pair lists of nonbonded interactions is the major problem with MD codes for SIMD machines, such that, generally, the full connectivity computation has been used. We present an algorithm, the global cut-off algorithm (GCA), which permits the use of pair lists on SIMD machines. GCA is based on a probabilistic approach and requires the cut-off condition to be simultaneously verified on all nodes of the machine. The MD code used was taken from the GROMOS package; only the routines involved in the pair lists and in the computation of nonbonded interactions were rewritten for a parallel architecture. The remaining calculations were performed on the host computer. The algorithm has been tested on Quadrics computers for configurations of 32, 128, and 512 processors and for systems of 4000, 8000, 15,000, and 30,000 particles. Quadrics was developed by Istituto Nazionale di Fisica Nucleare (INFN) and marketed by Alenia Spazio. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 685–694, 1998     

pmx: Automated protein structure and topology generation for alchemical perturbations

Computational protein design requires methods to accurately estimate free energy changes in protein stability or binding upon an amino acid mutation. From the different approaches available, molecular dynamics‐based alchemical free energy calculations are unique in their accuracy and solid theoretical basis. The challenge in using these methods lies in the need to generate hybrid structures and topologies representing two physical states of a system. A custom made hybrid topology may prove useful for a particular mutation of interest, however, a high throughput mutation analysis calls for a more general approach. In this work, we present an automated procedure to generate hybrid structures and topologies for the amino acid mutations in all commonly used force fields. The described software is compatible with the Gromacs simulation package. The mutation libraries are readily supported for five force fields, namely Amber99SB, Amber99SB*‐ILDN, OPLS‐AA/L, Charmm22*, and Charmm36. © 2014 The Authors Journal of Computational Chemistry Published by Wiley Periodicals, Inc.     

An improved rapid method for the determination of actinides in water

A new rapid method has been developed for the determination of Th, Pu, Np, U, Am and Cm isotopes in water samples of about 1 L. Actinides are pre-concentrated by co-precipitation with Ca phosphate, sequentially separated on stacked TEVA and TK221 cartridges and measured by alpha spectrometry. The TK221 extraction chromatographic resin contains i.e. CMPO and DGA extractants. It has been characterized by measuring the weight distribution ratios (D_w) of actinides which are higher than 1000 for all actinides in 3 M HNO₃. The method has been optimized, applied for the analysis of tap and seawater samples and validated by participating in an IAEA proficiency test. Chemical recoveries for all actinides are better than 50%. The method can be performed within one day.

     

Perturbative treatment of anharmonic vibrational effects on bond distances: An extended langevin dynamics method

In this work, we first review the perturbative treatment of an oscillator with cubic anharmonicity. It is shown that there is a quantum‐classical correspondence in terms of mean displacement, mean‐squared displacement, and the corresponding variance in the first‐order perturbation theory, provided that the amplitude of the classical oscillator is fixed at the zeroth‐order energy of quantum mechanics . This correspondence condition is realized by proposing the extended Langevin dynamics (XLD), where the key is to construct a proper driving force. It is assumed that the driving force adopts a simple harmonic form with its amplitude chosen according to , while the driving frequency chosen as the harmonic frequency. The latter can be improved by using the natural frequency of the system in response to the potential if its anharmonicity is strong. By comparing to the accurate numeric results from discrete variable representation calculations for a set of diatomic species, it is shown that the present method is able to capture the large part of anharmonicity, being competitive with the wave function‐based vibrational second‐order perturbation theory, for the whole frequency range from ～4400 cm^?1 (H₂) to ～160 cm^?1 (Na₂). XLD shows a substantial improvement over the classical molecular dynamics which ceases to work for hard mode when zero‐point energy effects are significant. © 2013 Wiley Periodicals, Inc.     

二溴卡宾产生方法的改进

研究了用超声和相转催化结合使溴仿与固体氢氧化钠反应生成二溴卡宾的改良方法. 用这一方法只需20-30分钟就可以在烯烃存在下获得高得率的1,1-二溴环丙烷, 并且具有更方便的纯化过程.     

Classical Reactive Molecular Dynamics Implementations: State of the Art

Reactive molecular dynamics (RMD) implementations equipped with force field approaches to simulate both the time evolution as well as chemical reactions of a broad class of materials are reviewed herein. We subdivide the RMD approaches developed during the last decade as well as older ones already reviewed in 1995 by Srivastava and Garrison and in 2000 by Brenner into two classes. The methods in the first RMD class rely on the use of a reaction cutoff distance and employ a sudden transition from the educts to the products. Due to their simplicity these methods are well suited to generate equilibrated atomistic or material‐specific coarse‐grained polymer structures. In connection with generic models they offer useful qualitative insight into polymerization reactions. The methods in the second RMD class are based on empirical reactive force fields and implement a smooth and continuous transition from the educts to the products. In this RMD class, the reactive potentials are based on many‐body or bond‐order force fields as well as on empirical standard force fields, such as CHARMM, AMBER or MM3 that are modified to become reactive. The aim with the more sophisticated implementations of the second RMD class is the investigation of the reaction kinetics and mechanisms as well as the evaluation of transition state geometries. Pure or hybrid ab initio, density functional, semi‐empirical, molecular mechanics, and Monte Carlo methods for which no time evolution of the chemical systems is achieved are excluded from the present review. So are molecular dynamics techniques coupled with quantum chemical methods for the treatment of the reactive regions, such as Car–Parinello molecular dynamics.     

FAMUSAMM: An algorithm for rapid evaluation of electrostatic interactions in molecular dynamics simulations

Within molecular dynamics simulations of protein–solvent systems the exact evaluation of long-range Coulomb interactions is computationally demanding and becomes prohibitive for large systems. Conventional truncation methods circumvent that computational problem, but are hampered by serious artifacts concerning structure and dynamics of the simulated systems. To avoid these artifacts we have developed an efficient and yet sufficiently accurate approximation scheme which combines the structure-adapted multipole method (SAMM) [C. Niedermeier and P. Tavan, J. Chem. Phys., 101 , 734 (1994)] with a multiple-time-step method. The computational effort for MD simulations required within our fast multiple-time-step structure-adapted multipole method (FAMUSAMM) scales linearly with the number of particles. For a system with 36,000 atoms we achieve a computational speed-up by a factor of 60 as compared with the exact evaluation of the Coulomb forces. Extended test simulations show that the applied approximations do not seriously affect structural or dynamical properties of the simulated systems. © 1997 John Wiley & Sons, Inc. J Comput Chem 18 : 1729–1749, 1997     

Development of hardware accelerator for molecular dynamics simulations: a computation board that calculates nonbonded interactions in cooperation with fast multipole method

Evaluation of long-range Coulombic interactions still represents a bottleneck in the molecular dynamics (MD) simulations of biological macromolecules. Despite the advent of sophisticated fast algorithms, such as the fast multipole method (FMM), accurate simulations still demand a great amount of computation time due to the accuracy/speed trade-off inherently involved in these algorithms. Unless higher order multipole expansions, which are extremely expensive to evaluate, are employed, a large amount of the execution time is still spent in directly calculating particle-particle interactions within the nearby region of each particle. To reduce this execution time for pair interactions, we developed a computation unit (board), called MD-Engine II, that calculates nonbonded pairwise interactions using a specially designed hardware. Four custom arithmetic-processors and a processor for memory manipulation ("particle processor") are mounted on the computation board. The arithmetic processors are responsible for calculation of the pair interactions. The particle processor plays a central role in realizing efficient cooperation with the FMM. The results of a series of 50-ps MD simulations of a protein-water system (50,764 atoms) indicated that a more stringent setting of accuracy in FMM computation, compared with those previously reported, was required for accurate simulations over long time periods. Such a level of accuracy was efficiently achieved using the cooperative calculations of the FMM and MD-Engine II. On an Alpha 21264 PC, the FMM computation at a moderate but tolerable level of accuracy was accelerated by a factor of 16.0 using three boards. At a high level of accuracy, the cooperative calculation achieved a 22.7-fold acceleration over the corresponding conventional FMM calculation. In the cooperative calculations of the FMM and MD-Engine II, it was possible to achieve more accurate computation at a comparable execution time by incorporating larger nearby regions.     

Calculation of free energy landscapes: A histogram reweighted metadynamics approach

We present an efficient method for the calculation of free energy landscapes. Our approach involves a history‐dependent bias potential, which is evaluated on a grid. The corresponding free energy landscape is constructed via a histogram reweighting procedure a posteriori. Because of the presence of the bias potential, it can be also used to accelerate rare events. In addition, the calculated free energy landscape is not restricted to the actual choice of collective variables and can in principle be extended to auxiliary variables of interest without further numerical effort. The applicability is shown for several examples. We present numerical results for the alanine dipeptide and the Met‐Enkephalin in explicit solution to illustrate our approach. Furthermore, we derive an empirical formula that allows the prediction of the computational cost for the ordinary metadynamics variant in comparison with our approach, which is validated by a dimensionless representation. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011     

Rationalization of the Superior Anticancer Activity of Phenanthriplatin: An In-Depth Computational Exploration

In the effort to overcome issues of toxicity and resistance inherent to treatment by the approved platinum anticancer agents, a large number of cisplatin variants continues today to be prepared and tested. One of the applied strategies is to use monofunctional platinum complexes that, unlike traditional bifunctional compounds, are able to form only a single covalent bond with nuclear DNA. Chirality, aquation reaction, interaction with guanine and N-acetyl methionine as well as, intercalation into, binding to and distortion of DNA have been investigated by using both quantum mechanical DFT and molecular dynamics computations aiming at contributing to the elucidation of the molecular mechanism underlying the significantly enhanced spectrum of activity of the monofunctional Pt^II drug phenanthriplatin. Analogous calculations have been performed in parallel for other two less potent monofunctional Pt^II drugs, pyriplatin and enpyriplatin, which show very different cytotoxic effects.     

Using the local elevation method to construct optimized umbrella sampling potentials: Calculation of the relative free energies and interconversion barriers of glucopyranose ring conformers in water

A method is proposed to combine the local elevation (LE) conformational searching and the umbrella sampling (US) conformational sampling approaches into a single local elevation umbrella sampling (LEUS) scheme for (explicit‐solvent) molecular dynamics (MD) simulations. In this approach, an initial (relatively short) LE build‐up (searching) phase is used to construct an optimized biasing potential within a subspace of conformationally relevant degrees of freedom, that is then used in a (comparatively longer) US sampling phase. This scheme dramatically enhances (in comparison with plain MD) the sampling power of MD simulations, taking advantage of the fact that the preoptimized biasing potential represents a reasonable approximation to the negative of the free energy surface in the considered conformational subspace. The method is applied to the calculation of the relative free energies of β‐D ‐glucopyranose ring conformers in water (within the GROMOS 45A4 force field). Different schemes to assign sampled conformational regions to distinct states are also compared. This approach, which bears some analogies with adaptive umbrella sampling and metadynamics (but within a very distinct implementation), is shown to be: (i) efficient (nearly all the computational effort is invested in the actual sampling phase rather than in searching and equilibration); (ii) robust (the method is only weakly sensitive to the details of the build‐up protocol, even for relatively short build‐up times); (iii) versatile (a LEUS biasing potential database could easily be preoptimized for small molecules and assembled on a fragment basis for larger ones). © 2009 Wiley Periodicals, Inc. J Comput Chem 2010     

MILCH SHAKE: An efficient method for constraint dynamics applied to alkanes

We describe a method to impose constraints in a molecular dynamics simulation. A technique developed to solve the special case of a linear topology (MILC SHAKE) is hybridized with the SHAKE algorithm. The methodology, which we term MILC‐hybridized SHAKE (or MILCH SHAKE), applies to more complex topologies. Here we consider the important case of all atom models of alkanes. Exploiting the mass difference between carbon and hydrogen we show that for higher alkanes MILCH SHAKE can be an order of magnitude faster than SHAKE. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009     

An improved HPTLC method for the rapid identification and quantification of sulfonamides

Summary R_f values of twenty therapeutic sulfonamides have been estimated in seven solvent systems. Based on these data a simple identification scheme was developed demanding only three solvent systems for complete separation.Quantification of corresponding fluorescamine derivatives at nanogram level was performed by the use of an TLC-scanner configured online with a microcomputer. Mathematical treatment of standard curves using the computer program Curve Fitter are discussed. Validity and reproducibility of results are compared with data obtained by HPLC and show good correlation.     

Comparison of thermodynamic integration and Bennett acceptance ratio for calculating relative protein‐ligand binding free energies

The performances of Bennett's acceptance ratio method and thermodynamic integration (TI) for the calculation of free energy differences in protein simulations are compared. For the latter, the standard trapezoidal rule, Simpson's rule, and Clenshaw‐Curtis integration are used as numerical integration methods. We evaluate the influence of the number and definition of intermediate states on the precision, accuracy, and efficiency of the free energy calculations. Our results show that non‐equidistantly spaced intermediate states are in some cases beneficial for the TI methods. Using several combinations of softness parameters and the λ power dependence, it is shown that these benefits are strongly dependent on the shape of the integrand. Although TI is more user‐friendly due to its simplicity, it was found that Bennett's acceptance ratio method is the more efficient method. It is also the least dependent on the choice of the intermediate states, making it more robust than TI. © 2013 Wiley Periodicals, Inc.     

硝酸酯增塑剂力学性能和界面相互作用的分子动力学模拟

运用分子动力学(MD)方法, 模拟研究了硝化甘油(NG)及其与硝化三乙二醇(TEGDN)组成的硝酸酯增塑剂的低温力学性能. 结果表明, NG/TEGDN混合体系较NG单组分体系的刚性减弱, 延展性和各向同性增强. 结合能计算和径向分布函数分析揭示了混合型硝酸酯增塑剂组分之间的相互作用及其本质.     

Force field evaluation for biomolecular simulation: free enthalpies of solvation of polar and apolar compounds in various solvents.

Recently, the GROMOS biomolecular force field parameter set 53A6--which has been parametrized to reproduce experimentally determined free enthalpies of hydration and solvation in cyclohexane of amino acid side-chain analogs--was presented. To investigate the transferability of the new parameter set, we calculated free enthalpies of solvation of a range of polar and apolar compounds in different solvents (methanol, dimethyl sulfoxide (DMSO), acetonitrile, and acetone) from molecular dynamics simulations using the GROMOS 53A6 force field. For methanol and DMSO, parameters were used that are available in the 53A6 parameter set. For acetonitrile, a recently developed model was taken and for acetone, two models available in literature were used. We found that trends in and values for the solvation free enthalpies are in satisfactory agreement with experiment, except for the solvation in acetone for which deviations from experiment can be explained in terms of the properties of the models used.