Lippert, Ross A; Predescu, Cristian; Ierardi, Douglas J; Mackenzie, Kenneth M; Eastwood, Michael P; Dror, Ron O; Shaw, David E
2013-10-28
In molecular dynamics simulations, control over temperature and pressure is typically achieved by augmenting the original system with additional dynamical variables to create a thermostat and a barostat, respectively. These variables generally evolve on timescales much longer than those of particle motion, but typical integrator implementations update the additional variables along with the particle positions and momenta at each time step. We present a framework that replaces the traditional integration procedure with separate barostat, thermostat, and Newtonian particle motion updates, allowing thermostat and barostat updates to be applied infrequently. Such infrequent updates provide a particularly substantial performance advantage for simulations parallelized across many computer processors, because thermostat and barostat updates typically require communication among all processors. Infrequent updates can also improve accuracy by alleviating certain sources of error associated with limited-precision arithmetic. In addition, separating the barostat, thermostat, and particle motion update steps reduces certain truncation errors, bringing the time-average pressure closer to its target value. Finally, this framework, which we have implemented on both general-purpose and special-purpose hardware, reduces software complexity and improves software modularity. PMID:24182003
Accurate lineshape spectroscopy and the Boltzmann constant
Truong, G.-W.; Anstie, J. D.; May, E. F.; Stace, T. M.; Luiten, A. N.
2015-01-01
Spectroscopy has an illustrious history delivering serendipitous discoveries and providing a stringent testbed for new physical predictions, including applications from trace materials detection, to understanding the atmospheres of stars and planets, and even constraining cosmological models. Reaching fundamental-noise limits permits optimal extraction of spectroscopic information from an absorption measurement. Here, we demonstrate a quantum-limited spectrometer that delivers high-precision measurements of the absorption lineshape. These measurements yield a very accurate measurement of the excited-state (6P1/2) hyperfine splitting in Cs, and reveals a breakdown in the well-known Voigt spectral profile. We develop a theoretical model that accounts for this breakdown, explaining the observations to within the shot-noise limit. Our model enables us to infer the thermal velocity dispersion of the Cs vapour with an uncertainty of 35 p.p.m. within an hour. This allows us to determine a value for Boltzmann's constant with a precision of 6 p.p.m., and an uncertainty of 71 p.p.m. PMID:26465085
Accurate lineshape spectroscopy and the Boltzmann constant.
Truong, G-W; Anstie, J D; May, E F; Stace, T M; Luiten, A N
2015-01-01
Spectroscopy has an illustrious history delivering serendipitous discoveries and providing a stringent testbed for new physical predictions, including applications from trace materials detection, to understanding the atmospheres of stars and planets, and even constraining cosmological models. Reaching fundamental-noise limits permits optimal extraction of spectroscopic information from an absorption measurement. Here, we demonstrate a quantum-limited spectrometer that delivers high-precision measurements of the absorption lineshape. These measurements yield a very accurate measurement of the excited-state (6P1/2) hyperfine splitting in Cs, and reveals a breakdown in the well-known Voigt spectral profile. We develop a theoretical model that accounts for this breakdown, explaining the observations to within the shot-noise limit. Our model enables us to infer the thermal velocity dispersion of the Cs vapour with an uncertainty of 35 p.p.m. within an hour. This allows us to determine a value for Boltzmann's constant with a precision of 6 p.p.m., and an uncertainty of 71 p.p.m. PMID:26465085
History and progress on accurate measurements of the Planck constant
NASA Astrophysics Data System (ADS)
Steiner, Richard
2013-01-01
The measurement of the Planck constant, h, is entering a new phase. The CODATA 2010 recommended value is 6.626 069 57 × 10-34 J s, but it has been a long road, and the trip is not over yet. Since its discovery as a fundamental physical constant to explain various effects in quantum theory, h has become especially important in defining standards for electrical measurements and soon, for mass determination. Measuring h in the International System of Units (SI) started as experimental attempts merely to prove its existence. Many decades passed while newer experiments measured physical effects that were the influence of h combined with other physical constants: elementary charge, e, and the Avogadro constant, NA. As experimental techniques improved, the precision of the value of h expanded. When the Josephson and quantum Hall theories led to new electronic devices, and a hundred year old experiment, the absolute ampere, was altered into a watt balance, h not only became vital in definitions for the volt and ohm units, but suddenly it could be measured directly and even more accurately. Finally, as measurement uncertainties now approach a few parts in 108 from the watt balance experiments and Avogadro determinations, its importance has been linked to a proposed redefinition of a kilogram unit of mass. The path to higher accuracy in measuring the value of h was not always an example of continuous progress. Since new measurements periodically led to changes in its accepted value and the corresponding SI units, it is helpful to see why there were bumps in the road and where the different branch lines of research joined in the effort. Recalling the bumps along this road will hopefully avoid their repetition in the upcoming SI redefinition debates. This paper begins with a brief history of the methods to measure a combination of fundamental constants, thus indirectly obtaining the Planck constant. The historical path is followed in the section describing how the improved
History and progress on accurate measurements of the Planck constant.
Steiner, Richard
2013-01-01
The measurement of the Planck constant, h, is entering a new phase. The CODATA 2010 recommended value is 6.626 069 57 × 10(-34) J s, but it has been a long road, and the trip is not over yet. Since its discovery as a fundamental physical constant to explain various effects in quantum theory, h has become especially important in defining standards for electrical measurements and soon, for mass determination. Measuring h in the International System of Units (SI) started as experimental attempts merely to prove its existence. Many decades passed while newer experiments measured physical effects that were the influence of h combined with other physical constants: elementary charge, e, and the Avogadro constant, N(A). As experimental techniques improved, the precision of the value of h expanded. When the Josephson and quantum Hall theories led to new electronic devices, and a hundred year old experiment, the absolute ampere, was altered into a watt balance, h not only became vital in definitions for the volt and ohm units, but suddenly it could be measured directly and even more accurately. Finally, as measurement uncertainties now approach a few parts in 10(8) from the watt balance experiments and Avogadro determinations, its importance has been linked to a proposed redefinition of a kilogram unit of mass. The path to higher accuracy in measuring the value of h was not always an example of continuous progress. Since new measurements periodically led to changes in its accepted value and the corresponding SI units, it is helpful to see why there were bumps in the road and where the different branch lines of research joined in the effort. Recalling the bumps along this road will hopefully avoid their repetition in the upcoming SI redefinition debates. This paper begins with a brief history of the methods to measure a combination of fundamental constants, thus indirectly obtaining the Planck constant. The historical path is followed in the section describing how the
Accurate Molecular Polarizabilities Based on Continuum Electrostatics
Truchon, Jean-François; Nicholls, Anthony; Iftimie, Radu I.; Roux, Benoît; Bayly, Christopher I.
2013-01-01
A novel approach for representing the intramolecular polarizability as a continuum dielectric is introduced to account for molecular electronic polarization. It is shown, using a finite-difference solution to the Poisson equation, that the Electronic Polarization from Internal Continuum (EPIC) model yields accurate gas-phase molecular polarizability tensors for a test set of 98 challenging molecules composed of heteroaromatics, alkanes and diatomics. The electronic polarization originates from a high intramolecular dielectric that produces polarizabilities consistent with B3LYP/aug-cc-pVTZ and experimental values when surrounded by vacuum dielectric. In contrast to other approaches to model electronic polarization, this simple model avoids the polarizability catastrophe and accurately calculates molecular anisotropy with the use of very few fitted parameters and without resorting to auxiliary sites or anisotropic atomic centers. On average, the unsigned error in the average polarizability and anisotropy compared to B3LYP are 2% and 5%, respectively. The correlation between the polarizability components from B3LYP and this approach lead to a R2 of 0.990 and a slope of 0.999. Even the F2 anisotropy, shown to be a difficult case for existing polarizability models, can be reproduced within 2% error. In addition to providing new parameters for a rapid method directly applicable to the calculation of polarizabilities, this work extends the widely used Poisson equation to areas where accurate molecular polarizabilities matter. PMID:23646034
Molecular dynamics at constant temperature and pressure
NASA Astrophysics Data System (ADS)
Toxvaerd, S.
1993-01-01
Algorithms for molecular dynamics (MD) at constant temperature and pressure are investigated. The ability to remain in a regular orbit in an intermittent chaotic regime is used as a criterion for long-time stability. A simple time-centered algorithm (leap frog) is found to be the most stable of the commonly used algorithms in MD. A model of N one-dimensional dimers with a double-well intermolecular potential, for which the distribution functions at constant temperature T and pressure P can be calculated, is used to investigate MD-NPT dynamics. A time-centered NPT algorithm is found to sample correctly and to be very robust with respect to volume scaling.
Molecular dynamics at constant Cauchy stress
NASA Astrophysics Data System (ADS)
Miller, Ronald E.; Tadmor, Ellad B.; Gibson, Joshua S.; Bernstein, Noam; Pavia, Fabio
2016-05-01
The Parrinello-Rahman algorithm for imposing a general state of stress in periodic molecular dynamics simulations is widely used in the literature and has been implemented in many readily available molecular dynamics codes. However, what is often overlooked is that this algorithm controls the second Piola-Kirchhoff stress as opposed to the true (Cauchy) stress. This can lead to misinterpretation of simulation results because (1) the true stress that is imposed during the simulation depends on the deformation of the periodic cell, (2) the true stress is potentially very different from the imposed second Piola-Kirchhoff stress, and (3) the true stress can vary significantly during the simulation even if the imposed second Piola-Kirchhoff is constant. We propose a simple modification to the algorithm that allows the true Cauchy stress to be controlled directly. We then demonstrate the efficacy of the new algorithm with the example of martensitic phase transformations under applied stress.
Molecular dynamics at constant Cauchy stress.
Miller, Ronald E; Tadmor, Ellad B; Gibson, Joshua S; Bernstein, Noam; Pavia, Fabio
2016-05-14
The Parrinello-Rahman algorithm for imposing a general state of stress in periodic molecular dynamics simulations is widely used in the literature and has been implemented in many readily available molecular dynamics codes. However, what is often overlooked is that this algorithm controls the second Piola-Kirchhoff stress as opposed to the true (Cauchy) stress. This can lead to misinterpretation of simulation results because (1) the true stress that is imposed during the simulation depends on the deformation of the periodic cell, (2) the true stress is potentially very different from the imposed second Piola-Kirchhoff stress, and (3) the true stress can vary significantly during the simulation even if the imposed second Piola-Kirchhoff is constant. We propose a simple modification to the algorithm that allows the true Cauchy stress to be controlled directly. We then demonstrate the efficacy of the new algorithm with the example of martensitic phase transformations under applied stress. PMID:27179471
NASA Astrophysics Data System (ADS)
Sow, P. L. T.; Merji, S.; Tokunaga, S. K.; Lemarchand, C.; Triki, M.; Borde, C.; Chardonnet, C.; Darquie, B.; Daussy, C.
2013-06-01
Accurate molecular spectroscopy in the mid-infrared region allows precision measurements of fundamental constants. For instance, measuring the linewidth of an isolated Doppler-broadened absorption line of ammonia around 10 μm enables a determination of the Boltzmann constant k_{{B}}. We report on our latest measurements. The main systematic effects, including the temperature control, will be discussed and an error budget will be presented in which the global uncertainty on systematic effects is at the level of a few ppm. This is valid provided that data is recorded under the optimized experimental conditions determined by the studies of systematic effects and provided that spectra are fitted to the speed-dependent Voigt profile, identified as the most suitable lineshape for our measurements. A determination of k_{{B}} by Doppler spectroscopy with a combined uncertainty of a few ppm is within reach. This is comparable to the best current uncertainty obtained using acoustic methods and would make a significant contribution to any new value of k_{{B}} determined by the CODATA. Furthermore, having multiple independent measurements at these accuracies opens the possibility of defining the Kelvin by fixing k_{{B}}, an exciting prospect considering the upcoming redefinition of the International System of Units (SI). C. Lemarchand, M. Triki, B. Darquié, C. J. Bordé, C. Chardonnet and C. Daussy, New J. Phys. 13, 073028 (2011). M. Triki, C. Lemarchand, B. Darquié, P. L. T. Sow, V. Roncin, C. Chardonnet, and C. Daussy, Phys. Rev. A 85, 062510 (2012).
Quick and accurate estimation of the elastic constants using the minimum image method
NASA Astrophysics Data System (ADS)
Tretiakov, Konstantin V.; Wojciechowski, Krzysztof W.
2015-04-01
A method for determining the elastic properties using the minimum image method (MIM) is proposed and tested on a model system of particles interacting by the Lennard-Jones (LJ) potential. The elastic constants of the LJ system are determined in the thermodynamic limit, N → ∞, using the Monte Carlo (MC) method in the NVT and NPT ensembles. The simulation results show that when determining the elastic constants, the contribution of long-range interactions cannot be ignored, because that would lead to erroneous results. In addition, the simulations have revealed that the inclusion of further interactions of each particle with all its minimum image neighbors even in case of small systems leads to results which are very close to the values of elastic constants in the thermodynamic limit. This enables one for a quick and accurate estimation of the elastic constants using very small samples.
Li, Rui; Ye, Hongfei; Zhang, Weisheng; Ma, Guojun; Su, Yewang
2015-01-01
Spring constant calibration of the atomic force microscope (AFM) cantilever is of fundamental importance for quantifying the force between the AFM cantilever tip and the sample. The calibration within the framework of thin plate theory undoubtedly has a higher accuracy and broader scope than that within the well-established beam theory. However, thin plate theory-based accurate analytic determination of the constant has been perceived as an extremely difficult issue. In this paper, we implement the thin plate theory-based analytic modeling for the static behavior of rectangular AFM cantilevers, which reveals that the three-dimensional effect and Poisson effect play important roles in accurate determination of the spring constants. A quantitative scaling law is found that the normalized spring constant depends only on the Poisson’s ratio, normalized dimension and normalized load coordinate. Both the literature and our refined finite element model validate the present results. The developed model is expected to serve as the benchmark for accurate calibration of rectangular AFM cantilevers. PMID:26510769
Li, Rui; Ye, Hongfei; Zhang, Weisheng; Ma, Guojun; Su, Yewang
2015-01-01
Spring constant calibration of the atomic force microscope (AFM) cantilever is of fundamental importance for quantifying the force between the AFM cantilever tip and the sample. The calibration within the framework of thin plate theory undoubtedly has a higher accuracy and broader scope than that within the well-established beam theory. However, thin plate theory-based accurate analytic determination of the constant has been perceived as an extremely difficult issue. In this paper, we implement the thin plate theory-based analytic modeling for the static behavior of rectangular AFM cantilevers, which reveals that the three-dimensional effect and Poisson effect play important roles in accurate determination of the spring constants. A quantitative scaling law is found that the normalized spring constant depends only on the Poisson's ratio, normalized dimension and normalized load coordinate. Both the literature and our refined finite element model validate the present results. The developed model is expected to serve as the benchmark for accurate calibration of rectangular AFM cantilevers. PMID:26510769
NASA Astrophysics Data System (ADS)
Li, Rui; Ye, Hongfei; Zhang, Weisheng; Ma, Guojun; Su, Yewang
2015-10-01
Spring constant calibration of the atomic force microscope (AFM) cantilever is of fundamental importance for quantifying the force between the AFM cantilever tip and the sample. The calibration within the framework of thin plate theory undoubtedly has a higher accuracy and broader scope than that within the well-established beam theory. However, thin plate theory-based accurate analytic determination of the constant has been perceived as an extremely difficult issue. In this paper, we implement the thin plate theory-based analytic modeling for the static behavior of rectangular AFM cantilevers, which reveals that the three-dimensional effect and Poisson effect play important roles in accurate determination of the spring constants. A quantitative scaling law is found that the normalized spring constant depends only on the Poisson’s ratio, normalized dimension and normalized load coordinate. Both the literature and our refined finite element model validate the present results. The developed model is expected to serve as the benchmark for accurate calibration of rectangular AFM cantilevers.
NASA Astrophysics Data System (ADS)
Gates, Richard S.; Osborn, William A.; Shaw, Gordon A.
2015-06-01
Calibration of the flexural spring constant for atomic force microscope (AFM) colloid probe cantilevers provides significant challenges. The presence of a large attached spherical added mass complicates many of the more common calibration techniques such as reference cantilever, Sader, and added mass. Even the most promising option, AFM thermal calibration, can encounter difficulties during the optical lever sensitivity measurement due to strong adhesion and friction between the sphere and a surface. This may cause buckling of the end of the cantilever and hysteresis in the approach-retract curves resulting in increased uncertainty in the calibration. Most recently, a laser Doppler vibrometry thermal method has been used to accurately calibrate the normal spring constant of a wide variety of tipped and tipless commercial cantilevers. This paper describes a variant of the technique, scanning laser Doppler vibrometry, optimized for colloid probe cantilevers and capable of spring constant calibration uncertainties near ±1%.
Accurate measurements of the dielectric constant of seawater at L band
NASA Astrophysics Data System (ADS)
Lang, Roger; Zhou, Yiwen; Utku, Cuneyt; Le Vine, David
2016-01-01
This paper describes measurements of the dielectric constant of seawater at a frequency of 1.413 GHz, the center of the protected band (i.e., passive use only) used in the measurement of sea surface salinity from space. The objective of the measurements is to accurately determine the complex dielectric constant of seawater as a function of salinity and temperature. A resonant cylindrical microwave cavity in transmission mode has been employed to make the measurements. The measurements are made using standard seawater at salinities of 30, 33, 35, and 38 practical salinity units over a range of temperatures from 0°C to 35°C in 5°C intervals. Repeated measurements have been made at each temperature and salinity. Mean values and standard deviations are then computed. The total error budget indicates that the real and imaginary parts of the dielectric constant have a combined standard uncertainty of about 0.3 over the range of salinities and temperatures considered. The measurements are compared with the dielectric constants obtained from the model functions of Klein and Swift and those of Meissner and Wentz. The biggest differences occur at low and high temperatures.
Accurate Measurements of the Dielectric Constant of Seawater at L Band
NASA Technical Reports Server (NTRS)
Lang, Roger; Zhou, Yiwen; Utku, Cuneyt; Le Vine, David
2016-01-01
This paper describes measurements of the dielectric constant of seawater at a frequency of 1.413 GHz, the center of the protected band (i.e., passive use only) used in the measurement of sea surface salinity from space. The objective of the measurements is to accurately determine the complex dielectric constant of seawater as a function of salinity and temperature. A resonant cylindrical microwave cavity in transmission mode has been employed to make the measurements. The measurements are made using standard seawater at salinities of 30, 33, 35, and 38 practical salinity units over a range of temperatures from 0 degree C to 35 degree C in 5 degree C intervals. Repeated measurements have been made at each temperature and salinity. Mean values and standard deviations are then computed. The total error budget indicates that the real and imaginary parts of the dielectric constant have a combined standard uncertainty of about 0.3 over the range of salinities and temperatures considered. The measurements are compared with the dielectric constants obtained from the model functions of Klein and Swift and those of Meissner and Wentz. The biggest differences occur at low and high temperatures.
Developing accurate molecular mechanics force fields for conjugated molecular systems.
Do, Hainam; Troisi, Alessandro
2015-10-14
A rapid method to parameterize the intramolecular component of classical force fields for complex conjugated molecules is proposed. The method is based on a procedure of force matching with a reference electronic structure calculation. It is particularly suitable for those applications where molecular dynamics simulations are used to generate structures that are therefore analysed by electronic structure methods, because it is possible to build force fields that are consistent with electronic structure calculations that follow classical simulations. Such applications are commonly encountered in organic electronics, spectroscopy of complex systems and photobiology (e.g. photosynthetic systems). We illustrate the method by parameterizing the force fields of a molecule used in molecular semiconductors (2,2-dicyanovinyl-capped S,N-heteropentacene or DCV-SN5), a polymeric semiconductor (thieno[3,2-b]thiophene-diketopyrrolopyrrole TT-DPP) and a chromophore embedded in a protein environment (15,16-dihydrobiliverdin or DBV) where several hundreds of parameters need to be optimized in parallel. PMID:26349916
Accurate Measurements of the Dielectric Constant of Seawater at L Band
NASA Technical Reports Server (NTRS)
Lang, Roger H.; Utku, Cuneyt; Tarkocin, Yalcin; LeVine, David M.
2010-01-01
This report describes measurements of the dielectric constant of seawater at a frequency of 1.413 GHz that is at the center of the L-Sand radiometric protected frequency spectrum. Aquarius will be sensing the sea surface salinity from space in this band. The objective of the project is to refine the model function for the dielectric constant as a function of salinity and temperature so that remote sensing measurements can be made with the accuracy needed to meet the measurement goals (0.2 psu) of the Aquarius mission. The measurements were made, using a microwave cavity operated in the transmission configuration. The cavity's temperature was accurately regulated to 0.02 C by immersing it in a temperature controlled bath of distilled water and ethanol glycol. Seawater had been purchased from Ocean Scientific International Limited (OS1L) at salinities of 30, 35 and 38 psu. Measurements of these seawater samples were then made over a range of temperatures, from l0 C to 35 C in 5 C intervals. Repeated measurements were made at each temperature and salinity, Mean values and standard deviations were then computed. Total error budgets indicated that the real and imaginary parts of the dielectric constant had a relative accuracy of about l%.
NASA Technical Reports Server (NTRS)
Lee, Timothy J.; Dateo, Christopher E.; Schwenke, David W.; Chaban, Galina M.
2005-01-01
Accurate quartic force fields have been determined for the CCH- and NH2- molecular anions using the singles and doubles coupled-cluster method that includes a perturbational estimate of the effects of connected triple excitations, CCSD(T). Very large one-particle basis sets have been used including diffuse functions and up through g-type functions. Correlation of the nitrogen and carbon core electrons has been included, as well as other "small" effects, such as the diagonal Born-Oppenheimer correction, and basis set extrapolation, and corrections for higher-order correlation effects and scalar relativistic effects. Fundamental vibrational frequencies have been computed using standard second-order perturbation theory as well as variational methods. Comparison with the available experimental data is presented and discussed. The implications of our research for the astronomical observation of molecular anions will be discussed.
Effect of molecular orientation on the elastic constants of polypropylene.
Kumar, S. R.; Renusch, D. P.; Grimsditch, M.; Materials Science Division; Amoco Polymers Research & Development
2000-03-07
The Brillouin spectroscopic measurements of elastic properties of polypropylene films fabricated by different processing techniques are described. We find that the elastic symmetry and the associated elastic constants are dependent on the molecular orientation brought about by the processing conditions used to produce the films. We have shown that Brillouin scattering techniques can successfully be used to track the molecular orientation induced by uniaxial stretching. We find a direct correspondence between the Brillouin measurements and optical birefringence measurements, illustrating that molecular orientation plays a dominant role in determining the mechanical anisotropy in these materials.
Huang, Xinchuan; Taylor, Peter R; Lee, Timothy J
2011-05-19
High levels of theory have been used to compute quartic force fields (QFFs) for the cyclic and linear forms of the C(3)H(3)(+) molecular cation, referred to as c-C(3)H(3)(+) and l-C(3)H(3)(+). Specifically, the singles and doubles coupled-cluster method that includes a perturbational estimate of connected triple excitations, CCSD(T), has been used in conjunction with extrapolation to the one-particle basis set limit, and corrections for scalar relativity and core correlation have been included. The QFFs have been used to compute highly accurate fundamental vibrational frequencies and other spectroscopic constants by use of both vibrational second-order perturbation theory and variational methods to solve the nuclear Schrödinger equation. Agreement between our best computed fundamental vibrational frequencies and recent infrared photodissociation experiments is reasonable for most bands, but there are a few exceptions. Possible sources for the discrepancies are discussed. We determine the energy difference between the cyclic and linear forms of C(3)H(3)(+), obtaining 27.9 kcal/mol at 0 K, which should be the most reliable available. It is expected that the fundamental vibrational frequencies and spectroscopic constants presented here for c-C(3)H(3)(+) and l-C(3)H(3)(+) are the most reliable available for the free gas-phase species, and it is hoped that these will be useful in the assignment of future high-resolution laboratory experiments or astronomical observations. PMID:21510653
NASA Technical Reports Server (NTRS)
Huang, Xinchuan; Taylor, Peter R.; Lee, Timothy J.
2011-01-01
High levels of theory have been used to compute quartic force fields (QFFs) for the cyclic and linear forms of the C H + molecular cation, referred to as c-C H + and I-C H +. Specifically the 33 3333 singles and doubles coupled-cluster method that includes a perturbational estimate of connected triple excitations, CCSD(T), has been used in conjunction with extrapolation to the one-particle basis set limit and corrections for scalar relativity and core correlation have been included. The QFFs have been used to compute highly accurate fundamental vibrational frequencies and other spectroscopic constants using both vibrational 2nd-order perturbation theory and variational methods to solve the nuclear Schroedinger equation. Agreement between our best computed fundamental vibrational frequencies and recent infrared photodissociation experiments is reasonable for most bands, but there are a few exceptions. Possible sources for the discrepancies are discussed. We determine the energy difference between the cyclic and linear forms of C H +, 33 obtaining 27.9 kcal/mol at 0 K, which should be the most reliable available. It is expected that the fundamental vibrational frequencies and spectroscopic constants presented here for c-C H + 33 and I-C H + are the most reliable available for the free gas-phase species and it is hoped that 33 these will be useful in the assignment of future high-resolution laboratory experiments or astronomical observations.
A robust and accurate formulation of molecular and colloidal electrostatics.
Sun, Qiang; Klaseboer, Evert; Chan, Derek Y C
2016-08-01
This paper presents a re-formulation of the boundary integral method for the Debye-Hückel model of molecular and colloidal electrostatics that removes the mathematical singularities that have to date been accepted as an intrinsic part of the conventional boundary integral equation method. The essence of the present boundary regularized integral equation formulation consists of subtracting a known solution from the conventional boundary integral method in such a way as to cancel out the singularities associated with the Green's function. This approach better reflects the non-singular physical behavior of the systems on boundaries with the benefits of the following: (i) the surface integrals can be evaluated accurately using quadrature without any need to devise special numerical integration procedures, (ii) being able to use quadratic or spline function surface elements to represent the surface more accurately and the variation of the functions within each element is represented to a consistent level of precision by appropriate interpolation functions, (iii) being able to calculate electric fields, even at boundaries, accurately and directly from the potential without having to solve hypersingular integral equations and this imparts high precision in calculating the Maxwell stress tensor and consequently, intermolecular or colloidal forces, (iv) a reliable way to handle geometric configurations in which different parts of the boundary can be very close together without being affected by numerical instabilities, therefore potentials, fields, and forces between surfaces can be found accurately at surface separations down to near contact, and (v) having the simplicity of a formulation that does not require complex algorithms to handle singularities will result in significant savings in coding effort and in the reduction of opportunities for coding errors. These advantages are illustrated using examples drawn from molecular and colloidal electrostatics. PMID:27497538
A robust and accurate formulation of molecular and colloidal electrostatics
NASA Astrophysics Data System (ADS)
Sun, Qiang; Klaseboer, Evert; Chan, Derek Y. C.
2016-08-01
This paper presents a re-formulation of the boundary integral method for the Debye-Hückel model of molecular and colloidal electrostatics that removes the mathematical singularities that have to date been accepted as an intrinsic part of the conventional boundary integral equation method. The essence of the present boundary regularized integral equation formulation consists of subtracting a known solution from the conventional boundary integral method in such a way as to cancel out the singularities associated with the Green's function. This approach better reflects the non-singular physical behavior of the systems on boundaries with the benefits of the following: (i) the surface integrals can be evaluated accurately using quadrature without any need to devise special numerical integration procedures, (ii) being able to use quadratic or spline function surface elements to represent the surface more accurately and the variation of the functions within each element is represented to a consistent level of precision by appropriate interpolation functions, (iii) being able to calculate electric fields, even at boundaries, accurately and directly from the potential without having to solve hypersingular integral equations and this imparts high precision in calculating the Maxwell stress tensor and consequently, intermolecular or colloidal forces, (iv) a reliable way to handle geometric configurations in which different parts of the boundary can be very close together without being affected by numerical instabilities, therefore potentials, fields, and forces between surfaces can be found accurately at surface separations down to near contact, and (v) having the simplicity of a formulation that does not require complex algorithms to handle singularities will result in significant savings in coding effort and in the reduction of opportunities for coding errors. These advantages are illustrated using examples drawn from molecular and colloidal electrostatics.
Molecular structure, spectral constants, and fermi resonances in chlorine nitrate
NASA Astrophysics Data System (ADS)
Petkie, Douglas T.; Butler, Rebecca A. H.; Helminger, Paul; De Lucia, Frank C.
2004-06-01
Chlorine nitrate has two low-lying vibrational modes that lead to a series of Fermi resonances in the 9 υ97 υ7 family of levels that include the 9 2⇔7 1 and 9 3⇔7 19 1 dyads and the 9 4⇔9 27 1⇔7 2 and 9 5⇔9 37 1⇔9 17 2 triads. These states, along with the ground and 9 1 vibrational states, have been previously analyzed with millimeter and submillimeter wave spectroscopy and provide a substantial body of data for the investigation of these resonances and their impact on calculated spectroscopic constants and structural parameters. Due to fitting indeterminacies, these previous analyses did not include the main Fermi resonance interaction term. Consequently, the fitted rotational constants are linear combinations of the unmixed rotational constants of the basis vibrational states. In this paper, we have calculated the contributions of the Fermi resonances to the observed rotational constants in a model that determines the vibrational-rotational constants, the Fermi term and the mixing between interacting vibrational states, the cubic potential constant ( φ997) that connects interacting levels through a Fermi resonance, and the inertial defects. These results agree with predictions from ab initio and harmonic force field calculations and provide further experimental information for the determination of the fundamental molecular properties of chlorine nitrate.
A general, accurate procedure for calculating molecular interaction force.
Yang, Pinghai; Qian, Xiaoping
2009-09-15
The determination of molecular interaction forces, e.g., van der Waals force, between macroscopic bodies is of fundamental importance for understanding sintering, adhesion and fracture processes. In this paper, we develop an accurate, general procedure for van der Waals force calculation. This approach extends a surface formulation that converts a six-dimensional (6D) volume integral into a 4D surface integral for the force calculation. It uses non-uniform rational B-spline (NURBS) surfaces to represent object surfaces. Surface integrals are then done on the parametric domain of the NURBS surfaces. It has combined advantages of NURBS surface representation and surface formulation, including (1) molecular interactions between arbitrary-shaped objects can be represented and evaluated by the NURBS model further common geometries such as spheres, cones, planes can be represented exactly and interaction forces are thus calculated accurately; (2) calculation efficiency is improved by converting the volume integral to the surface integral. This approach is implemented and validated via its comparison with analytical solutions for simple geometries. Calculation of van der Waals force between complex geometries with surface roughness is also demonstrated. A tutorial on the NURBS approach is given in Appendix A. PMID:19596335
Accurate Evaluation Method of Molecular Binding Affinity from Fluctuation Frequency
NASA Astrophysics Data System (ADS)
Hoshino, Tyuji; Iwamoto, Koji; Ode, Hirotaka; Ohdomari, Iwao
2008-05-01
Exact estimation of the molecular binding affinity is significantly important for drug discovery. The energy calculation is a direct method to compute the strength of the interaction between two molecules. This energetic approach is, however, not accurate enough to evaluate a slight difference in binding affinity when distinguishing a prospective substance from dozens of candidates for medicine. Hence more accurate estimation of drug efficacy in a computer is currently demanded. Previously we proposed a concept of estimating molecular binding affinity, focusing on the fluctuation at an interface between two molecules. The aim of this paper is to demonstrate the compatibility between the proposed computational technique and experimental measurements, through several examples for computer simulations of an association of human immunodeficiency virus type-1 (HIV-1) protease and its inhibitor (an example for a drug-enzyme binding), a complexation of an antigen and its antibody (an example for a protein-protein binding), and a combination of estrogen receptor and its ligand chemicals (an example for a ligand-receptor binding). The proposed affinity estimation has proven to be a promising technique in the advanced stage of the discovery and the design of drugs.
Molecular dynamics simulations of solutions at constant chemical potential
NASA Astrophysics Data System (ADS)
Perego, C.; Salvalaglio, M.; Parrinello, M.
2015-04-01
Molecular dynamics studies of chemical processes in solution are of great value in a wide spectrum of applications, which range from nano-technology to pharmaceutical chemistry. However, these calculations are affected by severe finite-size effects, such as the solution being depleted as the chemical process proceeds, which influence the outcome of the simulations. To overcome these limitations, one must allow the system to exchange molecules with a macroscopic reservoir, thus sampling a grand-canonical ensemble. Despite the fact that different remedies have been proposed, this still represents a key challenge in molecular simulations. In the present work, we propose the Constant Chemical Potential Molecular Dynamics (CμMD) method, which introduces an external force that controls the environment of the chemical process of interest. This external force, drawing molecules from a finite reservoir, maintains the chemical potential constant in the region where the process takes place. We have applied the CμMD method to the paradigmatic case of urea crystallization in aqueous solution. As a result, we have been able to study crystal growth dynamics under constant supersaturation conditions and to extract growth rates and free-energy barriers.
Ab Initio Simulation Beryllium in Solid Molecular Hydrogen: Elastic Constant
NASA Astrophysics Data System (ADS)
Guerrero, Carlo L.; Perlado, Jose M.
2016-03-01
In systems of inertial confinement fusion targets Deuterium-Tritium are manufactured with a solid layer, it must have specific properties to increase the efficiency of ignition. Currently there have been some proposals to model the phases of hydrogen isotopes and hence their high pressure, but these works do not allow explaining some of the structures present at the solid phase change effect of increased pressure. By means of simulation with first principles methods and Quantum Molecular Dynamics, we compare the structural difference of solid molecular hydrogen pure and solid molecular hydrogen with beryllium, watching beryllium inclusion in solid hydrogen matrix, we obtain several differences in mechanical properties, in particular elastic constants. For C11 the difference between hydrogen and hydrogen with beryllium is 37.56%. This may produce a non-uniform initial compression and decreased efficiency of ignition.
Microsatellites Are Molecular Clocks That Support Accurate Inferences about History
Mullikin, James C.; Patterson, Nick; Reich, David E.
2009-01-01
Microsatellite length mutations are often modeled using the generalized stepwise mutation process, which is a type of random walk. If this model is sufficiently accurate, one can estimate the coalescence time between alleles of a locus after a mathematical transformation of the allele lengths. When large-scale microsatellite genotyping first became possible, there was substantial interest in using this approach to make inferences about time and demography, but that interest has waned because it has not been possible to empirically validate the clock by comparing it with data in which the mutation process is well understood. We analyzed data from 783 microsatellite loci in human populations and 292 loci in chimpanzee populations, and compared them with up to one gigabase of aligned sequence data, where the molecular clock based upon nucleotide substitutions is believed to be reliable. We empirically demonstrate a remarkable linearity (r2 > 0.95) between the microsatellite average square distance statistic and sequence divergence. We demonstrate that microsatellites are accurate molecular clocks for coalescent times of at least 2 million years (My). We apply this insight to confirm that the African populations San, Biaka Pygmy, and Mbuti Pygmy have the deepest coalescent times among populations in the Human Genome Diversity Project. Furthermore, we show that microsatellites support unbiased estimates of population differentiation (FST) that are less subject to ascertainment bias than single nucleotide polymorphism (SNP) FST. These results raise the prospect of using microsatellite data sets to determine parameters of population history. When genotyped along with SNPs, microsatellite data can also be used to correct for SNP ascertainment bias. PMID:19221007
Towards Accurate Molecular Modeling of Plastic Bonded Explosives
NASA Astrophysics Data System (ADS)
Chantawansri, T. L.; Andzelm, J.; Taylor, D.; Byrd, E.; Rice, B.
2010-03-01
There is substantial interest in identifying the controlling factors that influence the susceptibility of polymer bonded explosives (PBXs) to accidental initiation. Numerous Molecular Dynamics (MD) simulations of PBXs using the COMPASS force field have been reported in recent years, where the validity of the force field in modeling the solid EM fill has been judged solely on its ability to reproduce lattice parameters, which is an insufficient metric. Performance of the COMPASS force field in modeling EMs and the polymeric binder has been assessed by calculating structural, thermal, and mechanical properties, where only fair agreement with experimental data is obtained. We performed MD simulations using the COMPASS force field for the polymer binder hydroxyl-terminated polybutadiene and five EMs: cyclotrimethylenetrinitramine, 1,3,5,7-tetranitro-1,3,5,7-tetra-azacyclo-octane, 2,4,6,8,10,12-hexantirohexaazazisowurzitane, 2,4,6-trinitro-1,3,5-benzenetriamine, and pentaerythritol tetranitate. Predicted EM crystallographic and molecular structural parameters, as well as calculated properties for the binder will be compared with experimental results for different simulation conditions. We also present novel simulation protocols, which improve agreement between experimental and computation results thus leading to the accurate modeling of PBXs.
Molecular adsorption at Pt(111). How accurate are DFT functionals?
Gautier, Sarah; Steinmann, Stephan N; Michel, Carine; Fleurat-Lessard, Paul; Sautet, Philippe
2015-11-21
Molecular chemisorption at a metal surface is a key step for many processes, such as catalysis, electrochemistry, surface treatment, tribology and friction. Modeling with density functional theory is largely used on these systems. From a detailed comparison with accurate micro-calorimetric data on ten systems (involving ethylene, cyclohexene, benzene, naphthalene, CO, O2, H2, methane, ethane), we study the accuracy, for chemisorption on Pt(111), of five exchange-correlation functionals including one generalized gradient approximation functional (PBE) and four functionals that take into account van der Waals interactions (optPBE-vdW, optB86b-vdW, BEEF-vdW, PBE-dDsC). If the functionals used provide very similar geometries and electronic structures, as shown by projected density of states, they give strikingly different results for the adsorption energy of molecules on Pt(111). Among the set of chemisorption data, the lowest mean absolute deviations (MAD) are obtained with the optPBE-vdW and PBE-dDsC functionals (∼0.2 eV) while PBE and optB86b-vdW give twice larger MAD (∼0.45 eV). BEEF-vdW is intermediate with a MAD of 0.33 eV. For laterally π-bound unsaturated hydrocarbons (cyclohexene, benzene, naphthalene) the PBE and the BEEF-vdW functionals are severally under-bound, while optPBE-vdW and PBE-dDsC provide a good match with experiments. Hence both the incorporation of van der Waals dispersive forces and the choice of the exchange functional have a key influence on the chemisorption energy. Vertically bound ethylidyne and CO are in contrast over-bound with all functionals, the best agreement being obtained with BEEF-vdW. None of the selected functionals hence provides a universally accurate treatment of chemisorption energies. PMID:26455444
Accurate calculations of the high-pressure elastic constants based on the first-principles
NASA Astrophysics Data System (ADS)
Wang, Chen-Ju; Gu, Jian-Bing; Kuang, Xiao-Yu; Yang, Xiang-Dong
2015-08-01
The energy term corresponding to the first order of the strain in Taylor series expansion of the energy with respect to strain is always ignored when high-pressure elastic constants are calculated. Whether the modus operandi would affect the results of the high-pressure elastic constants is still unsolved. To clarify this query, we calculate the high-pressure elastic constants of tantalum and rhenium when the energy term mentioned above is considered and neglected, respectively. Results show that the neglect of the energy term corresponding to the first order of the strain indeed would influence the veracity of the high-pressure elastic constants, and this influence becomes larger with pressure increasing. Therefore, the energy term corresponding to the first-order of the strain should be considered when the high-pressure elastic constants are calculated. Project supported by the National Natural Science Foundation of China (Grant No. 11274235), the Young Scientist Fund of the National Natural Science Foundation of China (Grant No. 11104190), and the Doctoral Education Fund of Education Ministry of China (Grant Nos. 20100181110086 and 20110181120112).
Song, Yunpeng; Wu, Sen; Xu, Linyan; Fu, Xing
2015-01-01
Measurement of force on a micro- or nano-Newton scale is important when exploring the mechanical properties of materials in the biophysics and nanomechanical fields. The atomic force microscope (AFM) is widely used in microforce measurement. The cantilever probe works as an AFM force sensor, and the spring constant of the cantilever is of great significance to the accuracy of the measurement results. This paper presents a normal spring constant calibration method with the combined use of an electromagnetic balance and a homemade AFM head. When the cantilever presses the balance, its deflection is detected through an optical lever integrated in the AFM head. Meanwhile, the corresponding bending force is recorded by the balance. Then the spring constant can be simply calculated using Hooke’s law. During the calibration, a feedback loop is applied to control the deflection of the cantilever. Errors that may affect the stability of the cantilever could be compensated rapidly. Five types of commercial cantilevers with different shapes, stiffness, and operating modes were chosen to evaluate the performance of our system. Based on the uncertainty analysis, the expanded relative standard uncertainties of the normal spring constant of most measured cantilevers are believed to be better than 2%. PMID:25763650
Stresses and elastic constants of crystalline sodium, from molecular dynamics
Schiferl, S.K.
1985-02-01
The stresses and the elastic constants of bcc sodium are calculated by molecular dynamics (MD) for temperatures to T = 340K. The total adiabatic potential of a system of sodium atoms is represented by pseudopotential model. The resulting expression has two terms: a large, strictly volume-dependent potential, plus a sum over ion pairs of a small, volume-dependent two-body potential. The stresses and the elastic constants are given as strain derivatives of the Helmholtz free energy. The resulting expressions involve canonical ensemble averages (and fluctuation averages) of the position and volume derivatives of the potential. An ensemble correction relates the results to MD equilibrium averages. Evaluation of the potential and its derivatives requires the calculation of integrals with infinite upper limits of integration, and integrand singularities. Methods for calculating these integrals and estimating the effects of integration errors are developed. A method is given for choosing initial conditions that relax quickly to a desired equilibrium state. Statistical methods developed earlier for MD data are extended to evaluate uncertainties in fluctuation averages, and to test for symmetry. 45 refs., 10 figs., 4 tabs.
Recent Results on the Accurate Measurements of the Dielectric Constant of Seawater at 1.413GHZ
NASA Technical Reports Server (NTRS)
Lang, R.H.; Tarkocin, Y.; Utku, C.; Le Vine, D.M.
2008-01-01
Measurements of the complex. dielectric constant of seawater at 30.00 psu, 35.00 psu and 38.27 psu over the temperature range from 5 C to 3 5 at 1.413 GHz are given and compared with the Klein-Swift results. A resonant cavity technique is used. The calibration constant used in the cavity perturbation formulas is determined experimentally using methanol and ethanediol (ethylene glycol) as reference liquids. Analysis of the data shows that the measurements are accurate to better than 1.0% in almost all cases studied.
Highly accurate analytical energy of a two-dimensional exciton in a constant magnetic field
NASA Astrophysics Data System (ADS)
Hoang, Ngoc-Tram D.; Nguyen, Duy-Anh P.; Hoang, Van-Hung; Le, Van-Hoang
2016-08-01
Explicit expressions are given for analytically describing the dependence of the energy of a two-dimensional exciton on magnetic field intensity. These expressions are highly accurate with the precision of up to three decimal places for the whole range of the magnetic field intensity. The results are shown for the ground state and some excited states; moreover, we have all formulae to obtain similar expressions of any excited state. Analysis of numerical results shows that the precision of three decimal places is maintained for the excited states with the principal quantum number of up to n=100.
NASA Astrophysics Data System (ADS)
Teale, Andrew M.; Lutnæs, Ola B.; Helgaker, Trygve; Tozer, David J.; Gauss, Jürgen
2013-01-01
Accurate sets of benchmark nuclear-magnetic-resonance shielding constants and spin-rotation constants are calculated using coupled-cluster singles-doubles (CCSD) theory and coupled-cluster singles-doubles-perturbative-triples [CCSD(T)] theory, in a variety of basis sets consisting of (rotational) London atomic orbitals. The accuracy of the calculated coupled-cluster constants is established by a careful comparison with experimental data, taking into account zero-point vibrational corrections. Coupled-cluster basis-set convergence is analyzed and extrapolation techniques are employed to estimate basis-set-limit quantities, thereby establishing an accurate benchmark data set. Together with the set provided for rotational g-tensors and magnetizabilities in our previous work [O. B. Lutnæs, A. M. Teale, T. Helgaker, D. J. Tozer, K. Ruud, and J. Gauss, J. Chem. Phys. 131, 144104 (2009)], 10.1063/1.3242081, it provides a substantial source of consistently calculated high-accuracy data on second-order magnetic response properties. The utility of this benchmark data set is demonstrated by examining a wide variety of Kohn-Sham exchange-correlation functionals for the calculation of these properties. None of the existing approximate functionals provide an accuracy competitive with that provided by CCSD or CCSD(T) theory. The need for a careful consideration of vibrational effects is clearly illustrated. Finally, the pure coupled-cluster results are compared with the results of Kohn-Sham calculations constrained to give the same electronic density. Routes to future improvements are discussed in light of this comparison.
Fang, Tao; Li, Wei; Gu, Fangwei; Li, Shuhua
2015-01-13
We extend the generalized energy-based fragmentation (GEBF) approach to molecular crystals under periodic boundary conditions (PBC), and we demonstrate the performance of the method for a variety of molecular crystals. With this approach, the lattice energy of a molecular crystal can be obtained from the energies of a series of embedded subsystems, which can be computed with existing advanced molecular quantum chemistry methods. The use of the field compensation method allows the method to take long-range electrostatic interaction of the infinite crystal environment into account and make the method almost translationally invariant. The computational cost of the present method scales linearly with the number of molecules in the unit cell. Illustrative applications demonstrate that the PBC-GEBF method with explicitly correlated quantum chemistry methods is capable of providing accurate descriptions on the lattice energies and structures for various types of molecular crystals. In addition, this approach can be employed to quantify the contributions of various intermolecular interactions to the theoretical lattice energy. Such qualitative understanding is very useful for rational design of molecular crystals. PMID:26574207
Constant pressure and temperature discrete-time Langevin molecular dynamics.
Grønbech-Jensen, Niels; Farago, Oded
2014-11-21
We present a new and improved method for simultaneous control of temperature and pressure in molecular dynamics simulations with periodic boundary conditions. The thermostat-barostat equations are built on our previously developed stochastic thermostat, which has been shown to provide correct statistical configurational sampling for any time step that yields stable trajectories. Here, we extend the method and develop a set of discrete-time equations of motion for both particle dynamics and system volume in order to seek pressure control that is insensitive to the choice of the numerical time step. The resulting method is simple, practical, and efficient. The method is demonstrated through direct numerical simulations of two characteristic model systems-a one-dimensional particle chain for which exact statistical results can be obtained and used as benchmarks, and a three-dimensional system of Lennard-Jones interacting particles simulated in both solid and liquid phases. The results, which are compared against the method of Kolb and Dünweg [J. Chem. Phys. 111, 4453 (1999)], show that the new method behaves according to the objective, namely that acquired statistical averages and fluctuations of configurational measures are accurate and robust against the chosen time step applied to the simulation. PMID:25416875
Constant pressure and temperature discrete-time Langevin molecular dynamics
Grønbech-Jensen, Niels; Farago, Oded
2014-11-21
We present a new and improved method for simultaneous control of temperature and pressure in molecular dynamics simulations with periodic boundary conditions. The thermostat-barostat equations are built on our previously developed stochastic thermostat, which has been shown to provide correct statistical configurational sampling for any time step that yields stable trajectories. Here, we extend the method and develop a set of discrete-time equations of motion for both particle dynamics and system volume in order to seek pressure control that is insensitive to the choice of the numerical time step. The resulting method is simple, practical, and efficient. The method is demonstrated through direct numerical simulations of two characteristic model systems—a one-dimensional particle chain for which exact statistical results can be obtained and used as benchmarks, and a three-dimensional system of Lennard-Jones interacting particles simulated in both solid and liquid phases. The results, which are compared against the method of Kolb and Dünweg [J. Chem. Phys. 111, 4453 (1999)], show that the new method behaves according to the objective, namely that acquired statistical averages and fluctuations of configurational measures are accurate and robust against the chosen time step applied to the simulation.
Accurate and predictive antibody repertoire profiling by molecular amplification fingerprinting
Khan, Tarik A.; Friedensohn, Simon; de Vries, Arthur R. Gorter; Straszewski, Jakub; Ruscheweyh, Hans-Joachim; Reddy, Sai T.
2016-01-01
High-throughput antibody repertoire sequencing (Ig-seq) provides quantitative molecular information on humoral immunity. However, Ig-seq is compromised by biases and errors introduced during library preparation and sequencing. By using synthetic antibody spike-in genes, we determined that primer bias from multiplex polymerase chain reaction (PCR) library preparation resulted in antibody frequencies with only 42 to 62% accuracy. Additionally, Ig-seq errors resulted in antibody diversity measurements being overestimated by up to 5000-fold. To rectify this, we developed molecular amplification fingerprinting (MAF), which uses unique molecular identifier (UID) tagging before and during multiplex PCR amplification, which enabled tagging of transcripts while accounting for PCR efficiency. Combined with a bioinformatic pipeline, MAF bias correction led to measurements of antibody frequencies with up to 99% accuracy. We also used MAF to correct PCR and sequencing errors, resulting in enhanced accuracy of full-length antibody diversity measurements, achieving 98 to 100% error correction. Using murine MAF-corrected data, we established a quantitative metric of recent clonal expansion—the intraclonal diversity index—which measures the number of unique transcripts associated with an antibody clone. We used this intraclonal diversity index along with antibody frequencies and somatic hypermutation to build a logistic regression model for prediction of the immunological status of clones. The model was able to predict clonal status with high confidence but only when using MAF error and bias corrected Ig-seq data. Improved accuracy by MAF provides the potential to greatly advance Ig-seq and its utility in immunology and biotechnology. PMID:26998518
Accurate and predictive antibody repertoire profiling by molecular amplification fingerprinting.
Khan, Tarik A; Friedensohn, Simon; Gorter de Vries, Arthur R; Straszewski, Jakub; Ruscheweyh, Hans-Joachim; Reddy, Sai T
2016-03-01
High-throughput antibody repertoire sequencing (Ig-seq) provides quantitative molecular information on humoral immunity. However, Ig-seq is compromised by biases and errors introduced during library preparation and sequencing. By using synthetic antibody spike-in genes, we determined that primer bias from multiplex polymerase chain reaction (PCR) library preparation resulted in antibody frequencies with only 42 to 62% accuracy. Additionally, Ig-seq errors resulted in antibody diversity measurements being overestimated by up to 5000-fold. To rectify this, we developed molecular amplification fingerprinting (MAF), which uses unique molecular identifier (UID) tagging before and during multiplex PCR amplification, which enabled tagging of transcripts while accounting for PCR efficiency. Combined with a bioinformatic pipeline, MAF bias correction led to measurements of antibody frequencies with up to 99% accuracy. We also used MAF to correct PCR and sequencing errors, resulting in enhanced accuracy of full-length antibody diversity measurements, achieving 98 to 100% error correction. Using murine MAF-corrected data, we established a quantitative metric of recent clonal expansion-the intraclonal diversity index-which measures the number of unique transcripts associated with an antibody clone. We used this intraclonal diversity index along with antibody frequencies and somatic hypermutation to build a logistic regression model for prediction of the immunological status of clones. The model was able to predict clonal status with high confidence but only when using MAF error and bias corrected Ig-seq data. Improved accuracy by MAF provides the potential to greatly advance Ig-seq and its utility in immunology and biotechnology. PMID:26998518
Accurate molecular classification of cancer using simple rules
Wang, Xiaosheng; Gotoh, Osamu
2009-01-01
Background One intractable problem with using microarray data analysis for cancer classification is how to reduce the extremely high-dimensionality gene feature data to remove the effects of noise. Feature selection is often used to address this problem by selecting informative genes from among thousands or tens of thousands of genes. However, most of the existing methods of microarray-based cancer classification utilize too many genes to achieve accurate classification, which often hampers the interpretability of the models. For a better understanding of the classification results, it is desirable to develop simpler rule-based models with as few marker genes as possible. Methods We screened a small number of informative single genes and gene pairs on the basis of their depended degrees proposed in rough sets. Applying the decision rules induced by the selected genes or gene pairs, we constructed cancer classifiers. We tested the efficacy of the classifiers by leave-one-out cross-validation (LOOCV) of training sets and classification of independent test sets. Results We applied our methods to five cancerous gene expression datasets: leukemia (acute lymphoblastic leukemia [ALL] vs. acute myeloid leukemia [AML]), lung cancer, prostate cancer, breast cancer, and leukemia (ALL vs. mixed-lineage leukemia [MLL] vs. AML). Accurate classification outcomes were obtained by utilizing just one or two genes. Some genes that correlated closely with the pathogenesis of relevant cancers were identified. In terms of both classification performance and algorithm simplicity, our approach outperformed or at least matched existing methods. Conclusion In cancerous gene expression datasets, a small number of genes, even one or two if selected correctly, is capable of achieving an ideal cancer classification effect. This finding also means that very simple rules may perform well for cancerous class prediction. PMID:19874631
Accurate and molecular-size-tolerant NMR quantitation of diverse components in solution
Okamura, Hideyasu; Nishimura, Hiroshi; Nagata, Takashi; Kigawa, Takanori; Watanabe, Takashi; Katahira, Masato
2016-01-01
Determining the amount of each component of interest in a mixture is a fundamental first step in characterizing the nature of the solution and to develop possible means of utilization of its components. Similarly, determining the composition of units in complex polymers, or polymer mixtures, is crucial. Although NMR is recognized as one of the most powerful methods to achieve this and is widely used in many fields, variation in the molecular sizes or the relative mobilities of components skews quantitation due to the size-dependent decay of magnetization. Here, a method to accurately determine the amount of each component by NMR was developed. This method was validated using a solution that contains biomass-related components in which the molecular sizes greatly differ. The method is also tolerant of other factors that skew quantitation such as variation in the one-bond C–H coupling constant. The developed method is the first and only way to reliably overcome the skewed quantitation caused by several different factors to provide basic information on the correct amount of each component in a solution. PMID:26883279
Williams, Sarah L; Blachly, Patrick G; McCammon, J Andrew
2011-12-01
A constant pH molecular dynamics method has been used in the blind prediction of pK(a) values of titratable residues in wild type and mutated structures of the Staphylococcal nuclease (SNase) protein. The predicted values have been subsequently compared to experimental values provided by the laboratory of García-Moreno. CpHMD performs well in predicting the pK(a) of solvent-exposed residues. For residues in the protein interior, the CpHMD method encounters some difficulties in reaching convergence and predicting the pK(a) values for residues having strong interactions with neighboring residues. These results show the need to accurately and sufficiently sample conformational space in order to obtain pK(a) values consistent with experimental results. PMID:22072520
Analyzing and Interpreting NMR Spin-Spin Coupling Constants Using Molecular Orbital Calculations
ERIC Educational Resources Information Center
Autschbach, Jochen; Le Guennic, Boris
2007-01-01
Molecular orbital plots are used to analyze and interpret NMR spin-spin coupling constants, also known as J coupling constants. Students have accepted the concept of contributions to molecular properties from individual orbitals without the requirement to provide explicit equations.
A Simple and Convenient Method of Multiple Linear Regression to Calculate Iodine Molecular Constants
ERIC Educational Resources Information Center
Cooper, Paul D.
2010-01-01
A new procedure using a student-friendly least-squares multiple linear-regression technique utilizing a function within Microsoft Excel is described that enables students to calculate molecular constants from the vibronic spectrum of iodine. This method is advantageous pedagogically as it calculates molecular constants for ground and excited…
Microcomputer Calculation of Equilibrium Constants from Molecular Parameters of Gases.
ERIC Educational Resources Information Center
Venugopalan, Mundiyath
1989-01-01
Lists a BASIC program which computes the equilibrium constant as a function of temperature. Suggests use by undergraduates taking a one-year calculus-based physical chemistry course. Notes the program provides for up to four species, typically two reactants and two products. (MVL)
Den, Takuya S.; Frey, Hans-Martin; Leutwyler, Samuel
2014-11-21
The gas-phase rotational motion of hexafluorobenzene has been measured in real time using femtosecond (fs) time-resolved rotational Raman coherence spectroscopy (RR-RCS) at T = 100 and 295 K. This four-wave mixing method allows to probe the rotation of non-polar gas-phase molecules with fs time resolution over times up to ∼5 ns. The ground state rotational constant of hexafluorobenzene is determined as B{sub 0} = 1029.740(28) MHz (2σ uncertainty) from RR-RCS transients measured in a pulsed seeded supersonic jet, where essentially only the v = 0 state is populated. Using this B{sub 0} value, RR-RCS measurements in a room temperature gas cell give the rotational constants B{sub v} of the five lowest-lying thermally populated vibrationally excited states ν{sub 7/8}, ν{sub 9}, ν{sub 11/12}, ν{sub 13}, and ν{sub 14/15}. Their B{sub v} constants differ from B{sub 0} by between −1.02 MHz and +2.23 MHz. Combining the B{sub 0} with the results of all-electron coupled-cluster CCSD(T) calculations of Demaison et al. [Mol. Phys. 111, 1539 (2013)] and of our own allow to determine the C-C and C-F semi-experimental equilibrium bond lengths r{sub e}(C-C) = 1.3866(3) Å and r{sub e}(C-F) = 1.3244(4) Å. These agree with the CCSD(T)/wCVQZ r{sub e} bond lengths calculated by Demaison et al. within ±0.0005 Å. We also calculate the semi-experimental thermally averaged bond lengths r{sub g}(C-C)=1.3907(3) Å and r{sub g}(C-F)=1.3250(4) Å. These are at least ten times more accurate than two sets of experimental gas-phase electron diffraction r{sub g} bond lengths measured in the 1960s.
Constant pH Molecular Dynamics of Proteins in Explicit Solvent with Proton Tautomerism
Goh, Garrett B.; Hulbert, Benjamin S.; Zhou, Huiqing; Brooks, Charles L.
2015-01-01
pH is a ubiquitous regulator of biological activity, including protein-folding, protein-protein interactions and enzymatic activity. Existing constant pH molecular dynamics (CPHMD) models that were developed to address questions related to the pH-dependent properties of proteins are largely based on implicit solvent models. However, implicit solvent models are known to underestimate the desolvation energy of buried charged residues, increasing the error associated with predictions that involve internal ionizable residue that are important in processes like hydrogen transport and electron transfer. Furthermore, discrete water and ions cannot be modeled in implicit solvent, which are important in systems like membrane proteins and ion channels. We report on an explicit solvent constant pH molecular dynamics framework based on multi-site λ-dynamics (CPHMDMSλD). In the CPHMDMSλD framework, we performed seamless alchemical transitions between protonation and tautomeric states using multi-site λ-dynamics, and designed novel biasing potentials to ensure that the physical end-states are predominantly sampled. We show that explicit solvent CPHMDMSλD simulations model realistic pH-dependent properties of proteins such as the Hen-Egg White Lysozyme (HEWL), binding domain of 2-oxoglutarate dehydrogenase (BBL) and N-terminal domain of ribosomal L9 (NTL9), and the pKa predictions are in excellent agreement with experimental values, with a RMSE ranging from 0.72 to 0.84 pKa units. With the recent development of the explicit solvent CPHMDMSλD framework for nucleic acids, accurate modeling of pH-dependent properties of both major class of biomolecules – proteins and nucleic acids is now possible. PMID:24375620
Efficient implementation of constant pH molecular dynamics on modern graphics processors.
Arthur, Evan J; Brooks, Charles L
2016-09-15
The treatment of pH sensitive ionization states for titratable residues in proteins is often omitted from molecular dynamics (MD) simulations. While static charge models can answer many questions regarding protein conformational equilibrium and protein-ligand interactions, pH-sensitive phenomena such as acid-activated chaperones and amyloidogenic protein aggregation are inaccessible to such models. Constant pH molecular dynamics (CPHMD) coupled with the Generalized Born with a Simple sWitching function (GBSW) implicit solvent model provide an accurate framework for simulating pH sensitive processes in biological systems. Although this combination has demonstrated success in predicting pKa values of protein structures, and in exploring dynamics of ionizable side-chains, its speed has been an impediment to routine application. The recent availability of low-cost graphics processing unit (GPU) chipsets with thousands of processing cores, together with the implementation of the accurate GBSW implicit solvent model on those chipsets (Arthur and Brooks, J. Comput. Chem. 2016, 37, 927), provide an opportunity to improve the speed of CPHMD and ionization modeling greatly. Here, we present a first implementation of GPU-enabled CPHMD within the CHARMM-OpenMM simulation package interface. Depending on the system size and nonbonded force cutoff parameters, we find speed increases of between one and three orders of magnitude. Additionally, the algorithm scales better with system size than the CPU-based algorithm, thus allowing for larger systems to be modeled in a cost effective manner. We anticipate that the improved performance of this methodology will open the door for broad-spread application of CPHMD in its modeling pH-mediated biological processes. © 2016 Wiley Periodicals, Inc. PMID:27405884
NASA Astrophysics Data System (ADS)
Yogurtcu, Osman N.; Johnson, Margaret E.
2015-08-01
The dynamics of association between diffusing and reacting molecular species are routinely quantified using simple rate-equation kinetics that assume both well-mixed concentrations of species and a single rate constant for parameterizing the binding rate. In two-dimensions (2D), however, even when systems are well-mixed, the assumption of a single characteristic rate constant for describing association is not generally accurate, due to the properties of diffusional searching in dimensions d ≤ 2. Establishing rigorous bounds for discriminating between 2D reactive systems that will be accurately described by rate equations with a single rate constant, and those that will not, is critical for both modeling and experimentally parameterizing binding reactions restricted to surfaces such as cellular membranes. We show here that in regimes of intrinsic reaction rate (ka) and diffusion (D) parameters ka/D > 0.05, a single rate constant cannot be fit to the dynamics of concentrations of associating species independently of the initial conditions. Instead, a more sophisticated multi-parametric description than rate-equations is necessary to robustly characterize bimolecular reactions from experiment. Our quantitative bounds derive from our new analysis of 2D rate-behavior predicted from Smoluchowski theory. Using a recently developed single particle reaction-diffusion algorithm we extend here to 2D, we are able to test and validate the predictions of Smoluchowski theory and several other theories of reversible reaction dynamics in 2D for the first time. Finally, our results also mean that simulations of reactive systems in 2D using rate equations must be undertaken with caution when reactions have ka/D > 0.05, regardless of the simulation volume. We introduce here a simple formula for an adaptive concentration dependent rate constant for these chemical kinetics simulations which improves on existing formulas to better capture non-equilibrium reaction dynamics from dilute
Chen, Wen-Hwa; Wu, Chun-Hung; Cheng, Hsien-Chie
2011-07-10
Nose-Hoover (NH) thermostat methods incorporated with molecular dynamics (MD) simulation have been widely used to simulate the instantaneous system temperature and feedback energy in a canonical ensemble. The method simply relates the kinetic energy to the system temperature via the particles' momenta based on the ideal gas law. However, when used in a tightly bound system such as solids, the method may suffer from deriving a lower system temperature and potentially inducing early breaking of atomic bonds at relatively high temperature due to the neglect of the effect of the potential energy of atoms based on solid state physics. In this paper, a modified NH thermostat method is proposed for solid system. The method takes into account the contribution of phonons by virtue of the vibrational energy of lattice and the zero-point energy, derived based on the Debye theory. Proof of the equivalence of the method and the canonical ensemble is first made. The modified NH thermostat is tested on different gold nanocrystals to characterize their melting point and constant volume specific heat, and also their size and temperature dependence. Results show that the modified NH method can give much more comparable results to both the literature experimental and theoretical data than the standard NH. Most importantly, the present model is the only one, among the six thermostat algorithms under comparison, that can accurately reproduce the experimental data and also the T{sup 3}-law at temperature below the Debye temperature, where the specific heat of a solid at constant volume is proportional to the cube of temperature.
Frictional Response of Molecularly Thin Liquid Polymer Films Subject to Constant Shear Stress
NASA Astrophysics Data System (ADS)
Tschirhart, Charles; Troian, Sandra
2014-03-01
Measurements of the frictional response of nanoscale viscous films are typically obtained using the surface force apparatus in which a fluid layer is confined between smooth solid substrates approaching at constant speed or force. The squeezing pressure causes lateral flow from which the shear viscosity can be deduced. Under these conditions however, molecularly thin films tend to solidify wholly or partially and estimates of the shear viscosity can exceed those in macroscale films by many orders of magnitude. This problem can be avoided altogether by examining the response of an initially flat, supported, free surface film subject to comparable values of surface shear stress by application of an external inert gas stream. This method was first conceived by Derjaguin in 1944; more recent studies by Mate et al. at IBM Almaden on complex polymeric systems have uncovered fluid layering and other interesting behaviors. The only drawback is that this alternative technique requires an accurate model for interface distortion. We report on ellipsometric measurements of ultrathin polymeric films in efforts to determine whether the usual interface equations for free surface films based purely on continuum models can be properly extended to nanoscale films. Supported by a Fred and Jean Felberg Fellowship and G. W. Housner Student Discovery Fund.
NASA Astrophysics Data System (ADS)
Richardi, Johannes; Krienke, Hartmut; Fries, Pascal H.
1997-07-01
Kirkwood factors, yielding dielectric constants, are calculated from pair correlation functions, which are numerical solutions of the hypernetted-chain approximation of molecular Ornstein-Zernike (MOZ) theory. The combined influence of the molecular polarizability and the hydrogen bond strength is investigated. Using a reasonable diameter for the hydrogen size in the amide group, the MOZ Kirkwood factors and dielectric constants are in good agreement with the experimental values. This is explained by the statistical correlations between the orientations of two near molecules. This is consistent with hydrogen bonds, forming networks in formamide and chains in N-methylformamide.
NASA Astrophysics Data System (ADS)
Orkin, V. L.; Khamaganov, V. G.; Martynova, L. E.; Kurylo, M. J.
2013-12-01
Reactions with hydroxyl radicals and photolysis are the main processes dictating the compound residence time in the atmosphere for a majority of trace gases. In case of very short lived compounds their reaction with OH dictates both the atmospheric lifetime and active halogen release. Therefore, the accuracy of OH kinetic data is of primary importance for the purpose of comprehensive atmospheric modeling of compound's impact on the atmosphere, such as in ozone depletion (ODP) and climate change (GWP). The currently recommended uncertainties of OH reaction rate constants (NASA/JPL Publications and IUPAC Publications) exceed 10% at room temperature for the majority of compounds to be larger at lower temperatures of atmospheric interest. Thus, uncertainties in the photochemical properties of potential and current atmospheric trace gases obtained under controlled laboratory conditions may constitute a major source of uncertainty in estimating the compound's environmental impact. We will present the higher accuracy results of OH reaction rate constant determinations between 220 K and 370 K. A statistical analysis of the data will be discussed. The high precision of kinetic measurements performed at low temperatures allows reliable determination of temperature dependences of the rate constants. This is especially important because we found that many OH reactions exhibit the curvature of the Arrhenius plots. A detailed inventory of sources of instrumental uncertainties related to our experiment proves a total uncertainty of the OH reaction rate constant to be as small as ~2-3%. The estimation of the atmospheric lifetime of a compound based on its OH reaction rate constant will be discussed.
NASA Astrophysics Data System (ADS)
Mozafari, E.; Shulumba, N.; Steneteg, P.; Alling, B.; Abrikosov, Igor A.
2016-08-01
We present a theoretical scheme to calculate the elastic constants of magnetic materials in the high-temperature paramagnetic state. Our approach is based on a combination of disordered local moments picture and ab initio molecular dynamics (DLM-MD). Moreover, we investigate a possibility to enhance the efficiency of the simulations of elastic properties using the recently introduced method: symmetry imposed force constant temperature-dependent effective potential (SIFC-TDEP). We have chosen cubic paramagnetic CrN as a model system. This is done due to its technological importance and its demonstrated strong coupling between magnetic and lattice degrees of freedom. We have studied the temperature-dependent single-crystal and polycrystalline elastic constants of paramagentic CrN up to 1200 K. The obtained results at T = 300 K agree well with the experimental values of polycrystalline elastic constants as well as the Poisson ratio at room temperature. We observe that the Young's modulus is strongly dependent on temperature, decreasing by ˜14 % from T = 300 K to 1200 K. In addition we have studied the elastic anisotropy of CrN as a function of temperature and we observe that CrN becomes substantially more isotropic as the temperature increases. We demonstrate that the use of Birch law may lead to substantial errors for calculations of temperature induced changes of elastic moduli. The proposed methodology can be used for accurate predictions of mechanical properties of magnetic materials at temperatures above their magnetic order-disorder phase transition.
Use of hydrophobic constants of molecular fragments for characterizing analytical systems
Tselik, E.I.; Polvektov, N.S.
1985-06-10
The authors attempt to clarify the applicability of the proposed hydrophobicity parameters to a description of the behavior of complex compounds with organic ligands in extractional systems, and to establish quantitative relationships between the properties of the complex and hydrophobicity of the ligand. It was found that the stability constants of the ionic associates of lanthanum, neodymium, and erbium with certain derivatives of salicylic acid, dihalogenated derivatives of 8-hydroxyquinoline, and Rhodamine B correlate with the hydrophobicity of the ligands. The quantitative expressions of these serve as empirical hydrophobic constants of molecular fragments of organic compounds.
Molecular dynamics simulation of vapour-liquid nucleation of water with constant energy
NASA Astrophysics Data System (ADS)
Duška, Michal; Němec, Tomáš; Hrubý, Jan; Vinš, Václav; Planková, Barbora
2015-05-01
The paper describes molecular dynamics study of nucleation of water in NVE ensemble. The numerical simulation was performed with the DL_POLY. The metastable steam consisting of 10976 water molecules with TIP4P/2005 potential was driven on the desired energy level by a simulation at constant temperature, and then the nucleation at constant energy was studied for several tens of nanoseconds, which was sufficient for clusters to evolve at hundred molecules size. The results were compared with the previously published results and the classical nucleation theory predictions.
Hansen, Katja; Biegler, Franziska; Ramakrishnan, Raghunathan; Pronobis, Wiktor; von Lilienfeld, O. Anatole; Müller, Klaus -Robert; Tkatchenko, Alexandre
2015-06-04
Simultaneously accurate and efficient prediction of molecular properties throughout chemical compound space is a critical ingredient toward rational compound design in chemical and pharmaceutical industries. Aiming toward this goal, we develop and apply a systematic hierarchy of efficient empirical methods to estimate atomization and total energies of molecules. These methods range from a simple sum over atoms, to addition of bond energies, to pairwise interatomic force fields, reaching to the more sophisticated machine learning approaches that are capable of describing collective interactions between many atoms or bonds. In the case of equilibrium molecular geometries, even simple pairwise force fields demonstratemore » prediction accuracy comparable to benchmark energies calculated using density functional theory with hybrid exchange-correlation functionals; however, accounting for the collective many-body interactions proves to be essential for approaching the “holy grail” of chemical accuracy of 1 kcal/mol for both equilibrium and out-of-equilibrium geometries. This remarkable accuracy is achieved by a vectorized representation of molecules (so-called Bag of Bonds model) that exhibits strong nonlocality in chemical space. The same representation allows us to predict accurate electronic properties of molecules, such as their polarizability and molecular frontier orbital energies.« less
Hansen, Katja; Biegler, Franziska; Ramakrishnan, Raghunathan; Pronobis, Wiktor; von Lilienfeld, O. Anatole; Müller, Klaus -Robert; Tkatchenko, Alexandre
2015-06-04
Simultaneously accurate and efficient prediction of molecular properties throughout chemical compound space is a critical ingredient toward rational compound design in chemical and pharmaceutical industries. Aiming toward this goal, we develop and apply a systematic hierarchy of efficient empirical methods to estimate atomization and total energies of molecules. These methods range from a simple sum over atoms, to addition of bond energies, to pairwise interatomic force fields, reaching to the more sophisticated machine learning approaches that are capable of describing collective interactions between many atoms or bonds. In the case of equilibrium molecular geometries, even simple pairwise force fields demonstrate prediction accuracy comparable to benchmark energies calculated using density functional theory with hybrid exchange-correlation functionals; however, accounting for the collective many-body interactions proves to be essential for approaching the “holy grail” of chemical accuracy of 1 kcal/mol for both equilibrium and out-of-equilibrium geometries. This remarkable accuracy is achieved by a vectorized representation of molecules (so-called Bag of Bonds model) that exhibits strong nonlocality in chemical space. The same representation allows us to predict accurate electronic properties of molecules, such as their polarizability and molecular frontier orbital energies.
Kim, Yong-Hyun; Kim, Ki-Hyun
2016-01-01
A novel technique is developed to determine the Henry's law constants (HLCs) of seven volatile fatty acids (VFAs) with significantly high solubility using a combined application of thermal desorber/gas chromatography/mass spectrometry (TD/GC/MS). In light of the strong sorptive properties of these semi-volatile organic compounds (SVOCs), their HLCs were determined by properly evaluating the fraction lost on the surface of the materials used to induce equilibrium (vial, gas-tight syringe, and sorption tube). To this end, a total of nine repeated experiments were conducted in a closed (static) system at three different gas/liquid volume ratios. The best estimates for HLCs (M/atm) were thus 7,200 (propionic acid), 4,700 (i-butyric acid), 4,400 (n-butyric acid), 2,700 (i-valeric acid), 2,400 (n-valeric acid), 1,000 (hexanoic acid), and 1,500 (heptanoic acid). The differences in the HLC values between this study and previous studies, if assessed in terms of the percent difference, ranged from 9.2% (n-valeric acid) to 55.7% (i-valeric acid). We overcame the main cause of errors encountered in previous studies by performing the proper correction of the sorptive losses of the SVOCs that inevitably took place, particularly on the walls of the equilibration systems (mainly the headspace vial and/or the glass tight syringe). PMID:26577086
Application of the G-JF discrete-time thermostat for fast and accurate molecular simulations
NASA Astrophysics Data System (ADS)
Grønbech-Jensen, Niels; Hayre, Natha Robert; Farago, Oded
2014-02-01
A new Langevin-Verlet thermostat that preserves the fluctuation-dissipation relationship for discrete time steps is applied to molecular modeling and tested against several popular suites (AMBER, GROMACS, LAMMPS) using a small molecule as an example that can be easily simulated by all three packages. Contrary to existing methods, the new thermostat exhibits no detectable changes in the sampling statistics as the time step is varied in the entire numerical stability range. The simple form of the method, which we express in the three common forms (Velocity-Explicit, Störmer-Verlet, and Leap-Frog), allows for easy implementation within existing molecular simulation packages to achieve faster and more accurate results with no cost in either computing time or programming complexity.
Grebner, Christoph; Becker, Johannes; Weber, Daniel; Bellinger, Daniel; Tafipolski, Maxim; Brückner, Charlotte; Engels, Bernd
2014-09-15
The presented program package, Conformational Analysis and Search Tool (CAST) allows the accurate treatment of large and flexible (macro) molecular systems. For the determination of thermally accessible minima CAST offers the newly developed TabuSearch algorithm, but algorithms such as Monte Carlo (MC), MC with minimization, and molecular dynamics are implemented as well. For the determination of reaction paths, CAST provides the PathOpt, the Nudge Elastic band, and the umbrella sampling approach. Access to free energies is possible through the free energy perturbation approach. Along with a number of standard force fields, a newly developed symmetry-adapted perturbation theory-based force field is included. Semiempirical computations are possible through DFTB+ and MOPAC interfaces. For calculations based on density functional theory, a Message Passing Interface (MPI) interface to the Graphics Processing Unit (GPU)-accelerated TeraChem program is available. The program is available on request. PMID:25056524
Romanov, V N; Cygan, R T; Myshakin, E M
2012-06-21
Naturally occurring clay minerals provide a distinctive material for carbon capture and carbon dioxide sequestration. Swelling clay minerals, such as the smectite variety, possess an aluminosilicate structure that is controlled by low-charge layers that readily expand to accommodate water molecules and, potentially, CO2. Recent experimental studies have demonstrated the efficacy of intercalating CO2 in the interlayer of layered clays, but little is known about the molecular mechanisms of the process and the extent of carbon capture as a function of clay charge and structure. A series of molecular dynamics simulations and vibrational analyses have been completed to assess the molecular interactions associated with incorporation of CO2 and H2O in the interlayer of montmorillonite clay and to help validate the models with experimental observation. An accurate and fully flexible set of interatomic potentials for CO2 is developed and combined with Clayff potentials to help evaluate the intercalation mechanism and examine the effect of molecular flexibility onthe diffusion rate of CO2 in water.
NASA Astrophysics Data System (ADS)
Sellers, Michael; Lisal, Martin; Brennan, John
2015-06-01
Investigating the ability of a molecular model to accurately represent a real material is crucial to model development and use. When the model simulates materials in extreme conditions, one such property worth evaluating is the phase transition point. However, phase transitions are often overlooked or approximated because of difficulty or inaccuracy when simulating them. Techniques such as super-heating or super-squeezing a material to induce a phase change suffer from inherent timescale limitations leading to ``over-driving,'' and dual-phase simulations require many long-time runs to seek out what frequently results in an inexact location of phase-coexistence. We present a compilation of methods for the determination of solid-solid and solid-liquid phase transition points through the accurate calculation of the chemical potential. The methods are applied to the Smith-Bharadwaj atomistic potential's representation of cyclotrimethylene trinitramine (RDX) to accurately determine its melting point (Tm) and the alpha to gamma solid phase transition pressure. We also determine Tm for a coarse-grain model of RDX, and compare its value to experiment and atomistic counterpart. All methods are employed via the LAMMPS simulator, resulting in 60-70 simulations that total 30-50 ns. Approved for public release. Distribution is unlimited.
NASA Astrophysics Data System (ADS)
Mills, Andrew A.; Ford, Kyle B.; Kreckel, Holger; Perera, Manori; Crabtree, Kyle N.; McCall, Benjamin J.
2009-06-01
With the advent of Herschel and SOFIA, laboratory methods capable of providing molecular rest frequencies in the terahertz and sub-millimeter regime are increasingly important. As of yet, it has been difficult to perform spectroscopy in this wavelength region due to the limited availability of radiation sources, optics, and detectors. Our goal is to provide accurate THz rest frequencies for molecular ions by combining previously recorded microwave transitions with combination differences obtained from high precision mid-IR spectroscopy. We are constructing a Sensitive Resolved Ion Beam Spectroscopy setup which will harness the benefits of kinematic compression in a molecular ion beam to enable very high resolution spectroscopy. This ion beam is interrogated by continuous-wave cavity ringdown spectroscopy using a home-made widely tunable difference frequency laser that utilizes two near-IR lasers and a periodically-poled lithium niobate crystal. Here, we report our efforts to optimize our ion beam spectrometer and to perform high-precision and high-accuracy frequency measurements using an optical frequency comb. footnote
A large catalog of accurate distances to molecular clouds from PS1 photometry
Schlafly, E. F.; Rix, H.-W.; Martin, N. F.; Green, G.; Finkbeiner, D. P.; Bell, E. F.; Burgett, W. S.; Chambers, K. C.; Hodapp, K. W.; Kaiser, N.; Magnier, E. A.; Tonry, J. L.; Draper, P. W.; Metcalfe, N.; Price, P. A.
2014-05-01
Distance measurements to molecular clouds are important but are often made separately for each cloud of interest, employing very different data and techniques. We present a large, homogeneous catalog of distances to molecular clouds, most of which are of unprecedented accuracy. We determine distances using optical photometry of stars along lines of sight toward these clouds, obtained from PanSTARRS-1. We simultaneously infer the reddenings and distances to these stars, tracking the full probability distribution function using a technique presented in Green et al. We fit these star-by-star measurements using a simple dust screen model to find the distance to each cloud. We thus estimate the distances to almost all of the clouds in the Magnani et al. catalog, as well as many other well-studied clouds, including Orion, Perseus, Taurus, Cepheus, Polaris, California, and Monoceros R2, avoiding only the inner Galaxy. Typical statistical uncertainties in the distances are 5%, though the systematic uncertainty stemming from the quality of our stellar models is about 10%. The resulting catalog is the largest catalog of accurate, directly measured distances to molecular clouds. Our distance estimates are generally consistent with available distance estimates from the literature, though in some cases the literature estimates are off by a factor of more than two.
Local Elastic Constants for Epoxy-Nanotube Composites from Molecular Dynamics Simulation
NASA Technical Reports Server (NTRS)
Frankland, S. J. V.; Gates, T. S.
2007-01-01
A method from molecular dynamics simulation is developed for determining local elastic constants of an epoxy/nanotube composite. The local values of C11, C33, K12, and K13 elastic constants are calculated for an epoxy/nanotube composite as a function of radial distance from the nanotube. While the results possess a significant amount of statistical uncertainty resulting from both the numerical analysis and the molecular fluctuations during the simulation, the following observations can be made. If the size of the region around the nanotube is increased from shells of 1 to 6 in thickness, then the scatter in the data reduces enough to observe trends. All the elastic constants determined are at a minimum 20 from the center of the nanotube. The C11, C33, and K12 follow similar trends as a function of radial distance from the nanotube. The K13 decreases greater distances from the nanotube and becomes negative which may be a symptom of the statistical averaging.
NASA Astrophysics Data System (ADS)
Garrison, Stephen L.
2005-07-01
The combination of molecular simulations and potentials obtained from quantum chemistry is shown to be able to provide reasonably accurate thermodynamic property predictions. Gibbs ensemble Monte Carlo simulations are used to understand the effects of small perturbations to various regions of the model Lennard-Jones 12-6 potential. However, when the phase behavior and second virial coefficient are scaled by the critical properties calculated for each potential, the results obey a corresponding states relation suggesting a non-uniqueness problem for interaction potentials fit to experimental phase behavior. Several variations of a procedure collectively referred to as quantum mechanical Hybrid Methods for Interaction Energies (HM-IE) are developed and used to accurately estimate interaction energies from CCSD(T) calculations with a large basis set in a computationally efficient manner for the neon-neon, acetylene-acetylene, and nitrogen-benzene systems. Using these results and methods, an ab initio, pairwise-additive, site-site potential for acetylene is determined and then improved using results from molecular simulations using this initial potential. The initial simulation results also indicate that a limited range of energies important for accurate phase behavior predictions. Second virial coefficients calculated from the improved potential indicate that one set of experimental data in the literature is likely erroneous. This prescription is then applied to methanethiol. Difficulties in modeling the effects of the lone pair electrons suggest that charges on the lone pair sites negatively impact the ability of the intermolecular potential to describe certain orientations, but that the lone pair sites may be necessary to reasonably duplicate the interaction energies for several orientations. Two possible methods for incorporating the effects of three-body interactions into simulations within the pairwise-additivity formulation are also developed. A low density
Elastic Constants of Superconducting MgB2 from Molecular Dynamics Simulations with Shell Model
NASA Astrophysics Data System (ADS)
Guo, Yun-Dong; Chen, Xiang-Rong; Yang, Xiang-Dong; Gou, Qing-Quan
2005-11-01
The elastic constants of superconducting MgB2 are calculated using a molecular dynamics method (MD) with shell model. The lattice parameters, five independent elastic constants, equations of state (EOS), Debye temperature, and bulk modulus of MgB2 are obtained. Meanwhile, the dependence of the bulk modulus B, the lattice parameters a and c, and the unit cell volume V on the applied pressure are presented. It is demonstrated that the method introduced here can well reproduce the experimental results with a reasonable accuracy. The project supported by National Natural Science Foundation of China under Grant No. 60436010 and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, the Ministry of Education of China under Grant No. 2004176-6-4
A molecular site-site integral equation that yields the dielectric constant
NASA Astrophysics Data System (ADS)
Dyer, Kippi M.; Perkyns, John S.; Stell, George; Pettitt, B. Montgomery
2008-09-01
Our recent derivation [K. M. Dyer et al., J. Chem. Phys. 127, 194506 (2007)] of a diagrammatically proper, site-site, integral equation theory using molecular angular expansions is extended to polar fluids. With the addition of atomic site charges we take advantage of the formal long-ranged potential field cancellations before renormalization to generate a set of numerically stable equations. Results for calculations in a minimal (spherical) angular basis set are presented for the radial distribution function, the first dipolar (110) projection, and the dielectric constant for two model diatomic systems. All results, when compared to experiment and simulation, are a significant quantitative and qualitative improvement over previous site-site theories. More importantly, the dielectric constant is not trivial and close to simulation and experiment.
Fast and accurate quantum molecular dynamics of dense plasmas across temperature regimes
Sjostrom, Travis; Daligault, Jerome
2014-10-10
Here, we develop and implement a new quantum molecular dynamics approximation that allows fast and accurate simulations of dense plasmas from cold to hot conditions. The method is based on a carefully designed orbital-free implementation of density functional theory. The results for hydrogen and aluminum are in very good agreement with Kohn-Sham (orbital-based) density functional theory and path integral Monte Carlo calculations for microscopic features such as the electron density as well as the equation of state. The present approach does not scale with temperature and hence extends to higher temperatures than is accessible in the Kohn-Sham method and lower temperatures than is accessible by path integral Monte Carlo calculations, while being significantly less computationally expensive than either of those two methods.
Fast and accurate quantum molecular dynamics of dense plasmas across temperature regimes
Sjostrom, Travis; Daligault, Jerome
2014-10-10
Here, we develop and implement a new quantum molecular dynamics approximation that allows fast and accurate simulations of dense plasmas from cold to hot conditions. The method is based on a carefully designed orbital-free implementation of density functional theory. The results for hydrogen and aluminum are in very good agreement with Kohn-Sham (orbital-based) density functional theory and path integral Monte Carlo calculations for microscopic features such as the electron density as well as the equation of state. The present approach does not scale with temperature and hence extends to higher temperatures than is accessible in the Kohn-Sham method and lowermore » temperatures than is accessible by path integral Monte Carlo calculations, while being significantly less computationally expensive than either of those two methods.« less
Accurate force fields and methods for modelling organic molecular crystals at finite temperatures.
Nyman, Jonas; Pundyke, Orla Sheehan; Day, Graeme M
2016-06-21
We present an assessment of the performance of several force fields for modelling intermolecular interactions in organic molecular crystals using the X23 benchmark set. The performance of the force fields is compared to several popular dispersion corrected density functional methods. In addition, we present our implementation of lattice vibrational free energy calculations in the quasi-harmonic approximation, using several methods to account for phonon dispersion. This allows us to also benchmark the force fields' reproduction of finite temperature crystal structures. The results demonstrate that anisotropic atom-atom multipole-based force fields can be as accurate as several popular DFT-D methods, but have errors 2-3 times larger than the current best DFT-D methods. The largest error in the examined force fields is a systematic underestimation of the (absolute) lattice energy. PMID:27230942
Spinelli, Orietta; Rambaldi, Alessandro; Rigo, Francesca; Zanghì, Pamela; D'Agostini, Elena; Amicarelli, Giulia; Colotta, Francesco; Divona, Mariadomenica; Ciardi, Claudia; Coco, Francesco Lo; Minnucci, Giulia
2015-01-01
The diagnostic work-up of acute promyelocytic leukemia (APL) includes the cytogenetic demonstration of the t(15;17) translocation and/or the PML-RARA chimeric transcript by RQ-PCR or RT-PCR. This latter assays provide suitable results in 3-6 hours. We describe here two new, rapid and specific assays that detect PML-RARA transcripts, based on the RT-QLAMP (Reverse Transcription-Quenching Loop-mediated Isothermal Amplification) technology in which RNA retrotranscription and cDNA amplification are carried out in a single tube with one enzyme at one temperature, in fluorescence and real time format. A single tube triplex assay detects bcr1 and bcr3 PML-RARA transcripts along with GUS housekeeping gene. A single tube duplex assay detects bcr2 and GUSB. In 73 APL cases, these assays detected in 16 minutes bcr1, bcr2 and bcr3 transcripts. All 81 non-APL samples were negative by RT-QLAMP for chimeric transcripts whereas GUSB was detectable. In 11 APL patients in which RT-PCR yielded equivocal breakpoint type results, RT-QLAMP assays unequivocally and accurately defined the breakpoint type (as confirmed by sequencing). Furthermore, RT-QLAMP could amplify two bcr2 transcripts with particularly extended PML exon 6 deletions not amplified by RQ-PCR. RT-QLAMP reproducible sensitivity is 10−3 for bcr1 and bcr3 and 10−2 for bcr2 thus making this assay particularly attractive at diagnosis and leaving RQ-PCR for the molecular monitoring of minimal residual disease during the follow up. In conclusion, PML-RARA RT-QLAMP compared to RT-PCR or RQ-PCR is a valid improvement to perform rapid, simple and accurate molecular diagnosis of APL. PMID:25815362
Surface electron density models for accurate ab initio molecular dynamics with electronic friction
NASA Astrophysics Data System (ADS)
Novko, D.; Blanco-Rey, M.; Alducin, M.; Juaristi, J. I.
2016-06-01
Ab initio molecular dynamics with electronic friction (AIMDEF) is a valuable methodology to study the interaction of atomic particles with metal surfaces. This method, in which the effect of low-energy electron-hole (e-h) pair excitations is treated within the local density friction approximation (LDFA) [Juaristi et al., Phys. Rev. Lett. 100, 116102 (2008), 10.1103/PhysRevLett.100.116102], can provide an accurate description of both e-h pair and phonon excitations. In practice, its applicability becomes a complicated task in those situations of substantial surface atoms displacements because the LDFA requires the knowledge at each integration step of the bare surface electron density. In this work, we propose three different methods of calculating on-the-fly the electron density of the distorted surface and we discuss their suitability under typical surface distortions. The investigated methods are used in AIMDEF simulations for three illustrative adsorption cases, namely, dissociated H2 on Pd(100), N on Ag(111), and N2 on Fe(110). Our AIMDEF calculations performed with the three approaches highlight the importance of going beyond the frozen surface density to accurately describe the energy released into e-h pair excitations in case of large surface atom displacements.
PyVCI: A flexible open-source code for calculating accurate molecular infrared spectra
NASA Astrophysics Data System (ADS)
Sibaev, Marat; Crittenden, Deborah L.
2016-06-01
The PyVCI program package is a general purpose open-source code for simulating accurate molecular spectra, based upon force field expansions of the potential energy surface in normal mode coordinates. It includes harmonic normal coordinate analysis and vibrational configuration interaction (VCI) algorithms, implemented primarily in Python for accessibility but with time-consuming routines written in C. Coriolis coupling terms may be optionally included in the vibrational Hamiltonian. Non-negligible VCI matrix elements are stored in sparse matrix format to alleviate the diagonalization problem. CPU and memory requirements may be further controlled by algorithmic choices and/or numerical screening procedures, and recommended values are established by benchmarking using a test set of 44 molecules for which accurate analytical potential energy surfaces are available. Force fields in normal mode coordinates are obtained from the PyPES library of high quality analytical potential energy surfaces (to 6th order) or by numerical differentiation of analytic second derivatives generated using the GAMESS quantum chemical program package (to 4th order).
NASA Astrophysics Data System (ADS)
Orkin, V. L.; Khamaganov, V. G.; Martynova, L. E.; Kurylo, M. J.
2012-12-01
The emissions of halogenated (Cl, Br containing) organics of both natural and anthropogenic origin contribute to the balance of and changes in the stratospheric ozone concentration. The associated chemical cycles are initiated by the photochemical decomposition of the portion of source gases that reaches the stratosphere. Reactions with hydroxyl radicals and photolysis are the main processes dictating the compound lifetime in the troposphere and release of active halogen in the stratosphere for a majority of halogen source gases. Therefore, the accuracy of photochemical data is of primary importance for the purpose of comprehensive atmospheric modeling and for simplified kinetic estimations of global impacts on the atmosphere, such as in ozone depletion (i.e., the Ozone Depletion Potential, ODP) and climate change (i.e., the Global Warming Potential, GWP). The sources of critically evaluated photochemical data for atmospheric modeling, NASA/JPL Publications and IUPAC Publications, recommend uncertainties within 10%-60% for the majority of OH reaction rate constants with only a few cases where uncertainties lie at the low end of this range. These uncertainties can be somewhat conservative because evaluations are based on the data from various laboratories obtained during the last few decades. Nevertheless, even the authors of the original experimental works rarely estimate the total combined uncertainties of the published OH reaction rate constants to be less than ca. 10%. Thus, uncertainties in the photochemical properties of potential and current atmospheric trace gases obtained under controlled laboratory conditions still may constitute a major source of uncertainty in estimating the compound's environmental impact. One of the purposes of the presentation is to illustrate the potential for obtaining accurate laboratory measurements of the OH reaction rate constant over the temperature range of atmospheric interest. A detailed inventory of accountable sources of
Protocols Utilizing Constant pH Molecular Dynamics to Compute pH-Dependent Binding Free Energies
2015-01-01
In protein–ligand binding, the electrostatic environments of the two binding partners may vary significantly in bound and unbound states, which may lead to protonation changes upon binding. In cases where ligand binding results in a net uptake or release of protons, the free energy of binding is pH-dependent. Nevertheless, conventional free energy calculations and molecular docking protocols typically do not rigorously account for changes in protonation that may occur upon ligand binding. To address these shortcomings, we present a simple methodology based on Wyman’s binding polynomial formalism to account for the pH dependence of binding free energies and demonstrate its use on cucurbit[7]uril (CB[7]) host–guest systems. Using constant pH molecular dynamics and a reference binding free energy that is taken either from experiment or from thermodynamic integration computations, the pH-dependent binding free energy is determined. This computational protocol accurately captures the large pKa shifts observed experimentally upon CB[7]:guest association and reproduces experimental binding free energies at different levels of pH. We show that incorrect assignment of fixed protonation states in free energy computations can give errors of >2 kcal/mol in these host–guest systems. Use of the methods presented here avoids such errors, thus suggesting their utility in computing proton-linked binding free energies for protein–ligand complexes. PMID:25134690
Casciola, Maura; Kasimova, Marina A; Rems, Lea; Zullino, Sara; Apollonio, Francesca; Tarek, Mounir
2016-06-01
Molecular dynamics (MD) simulations have become a powerful tool to study electroporation (EP) in atomic detail. In the last decade, numerous MD studies have been conducted to model the effect of pulsed electric fields on membranes, providing molecular models of the EP process of lipid bilayers. Here we extend these investigations by modeling for the first time conditions comparable to experiments using long (μs-ms) low intensity (~kV/cm) pulses, by studying the characteristics of pores formed in lipid bilayers maintained at a constant surface tension and subject to constant charge imbalance. This enables the evaluation of structural (size) and electrical (conductance) properties of the pores formed, providing information hardly accessible directly by experiments. Extensive simulations of EP of simple phosphatidylcholine bilayers in 1M NaCl show that hydrophilic pores with stable radii (1-2.5nm) form under transmembrane voltages between 420 and 630mV, allowing for ionic conductance in the range of 6.4-29.5nS. We discuss in particular these findings and characterize both convergence and size effects in the MD simulations. We further extend these studies in a follow-up paper (Rems et al., Bioelectrochemistry, Submitted), by proposing an improved continuum model of pore conductance consistent with the results from the MD simulations. PMID:26883056
Partial hessian fitting for determining force constant parameters in molecular mechanics.
Wang, Ruixing; Ozhgibesov, Mikhail; Hirao, Hajime
2016-10-01
We present a new protocol for deriving force constant parameters that are used in molecular mechanics (MM) force fields to describe the bond-stretching, angle-bending, and dihedral terms. A 3 × 3 partial matrix is chosen from the MM Hessian matrix in Cartesian coordinates according to a simple rule and made as close as possible to the corresponding partial Hessian matrix computed using quantum mechanics (QM). This partial Hessian fitting (PHF) is done analytically and thus rapidly in a least-squares sense, yielding force constant parameters as the output. We herein apply this approach to derive force constant parameters for the AMBER-type energy expression. Test calculations on several different molecules show good performance of the PHF parameter sets in terms of how well they can reproduce QM-calculated frequencies. When soft bonds are involved in the target molecule as in the case of secondary building units of metal-organic frameworks, the MM-optimized geometry sometimes deviates significantly from the QM-optimized one. We show that this problem is rectified effectively by use of a simple procedure called Katachi that modifies the equilibrium bond distances and angles in bond-stretching and angle-bending terms. © 2016 Wiley Periodicals, Inc. PMID:27497261
NASA Astrophysics Data System (ADS)
Costandy, Joseph; Michalis, Vasileios K.; Tsimpanogiannis, Ioannis N.; Stubos, Athanassios K.; Economou, Ioannis G.
2016-03-01
We introduce a simple correction to the calculation of the lattice constants of fully occupied structure sI methane or carbon dioxide pure hydrates that are obtained from classical molecular dynamics simulations using the TIP4PQ/2005 water force field. The obtained corrected lattice constants are subsequently used in order to obtain isobaric thermal expansion coefficients of the pure gas hydrates that exhibit a trend that is significantly closer to the experimental behavior than previously reported classical molecular dynamics studies.
NASA Astrophysics Data System (ADS)
Cheng, Chi Y.; Ryley, Matthew S.; Peach, Michael J. G.; Tozer, David J.; Helgaker, Trygve; Teale, Andrew M.
2015-07-01
The Tamm-Dancoff approximation (TDA) can be applied to the computation of excitation energies using time-dependent Hartree-Fock (TD-HF) and time-dependent density-functional theory (TD-DFT). In addition to simplifying the resulting response equations, the TDA has been shown to significantly improve the calculation of triplet excitation energies in these theories, largely overcoming issues associated with triplet instabilities of the underlying reference wave functions. Here, we examine the application of the TDA to the calculation of another response property involving triplet perturbations, namely the indirect nuclear spin-spin coupling constant. Particular attention is paid to the accuracy of the triplet spin-dipole and Fermi-contact components. The application of the TDA in HF calculations leads to vastly improved results. For DFT calculations, the TDA delivers improved stability with respect to geometrical variations but does not deliver higher accuracy close to equilibrium geometries. These observations are rationalised in terms of the ground- and excited-state potential energy surfaces and, in particular, the severity of the triplet instabilities associated with each method. A notable feature of the DFT results within the TDA is their similarity across a wide range of different functionals. The uniformity of the TDA results suggests that some conventional evaluations may exploit error cancellations between approximations in the functional forms and those arising from triplet instabilities. The importance of an accurate treatment of correlation for evaluating spin-spin coupling constants is highlighted by this comparison.
Accurate calculation of binding energies for molecular clusters - Assessment of different models
NASA Astrophysics Data System (ADS)
Friedrich, Joachim; Fiedler, Benjamin
2016-06-01
In this work we test different strategies to compute high-level benchmark energies for medium-sized molecular clusters. We use the incremental scheme to obtain CCSD(T)/CBS energies for our test set and carefully validate the accuracy for binding energies by statistical measures. The local errors of the incremental scheme are <1 kJ/mol. Since they are smaller than the basis set errors, we obtain higher total accuracy due to the applicability of larger basis sets. The final CCSD(T)/CBS benchmark values are ΔE = - 278.01 kJ/mol for (H2O)10, ΔE = - 221.64 kJ/mol for (HF)10, ΔE = - 45.63 kJ/mol for (CH4)10, ΔE = - 19.52 kJ/mol for (H2)20 and ΔE = - 7.38 kJ/mol for (H2)10 . Furthermore we test state-of-the-art wave-function-based and DFT methods. Our benchmark data will be very useful for critical validations of new methods. We find focal-point-methods for estimating CCSD(T)/CBS energies to be highly accurate and efficient. For foQ-i3CCSD(T)-MP2/TZ we get a mean error of 0.34 kJ/mol and a standard deviation of 0.39 kJ/mol.
Lee, M.W.; Meuwly, M.
2013-01-01
The evaluation of hydration free energies is a sensitive test to assess force fields used in atomistic simulations. We showed recently that the vibrational relaxation times, 1D- and 2D-infrared spectroscopies for CN(-) in water can be quantitatively described from molecular dynamics (MD) simulations with multipolar force fields and slightly enlarged van der Waals radii for the C- and N-atoms. To validate such an approach, the present work investigates the solvation free energy of cyanide in water using MD simulations with accurate multipolar electrostatics. It is found that larger van der Waals radii are indeed necessary to obtain results close to the experimental values when a multipolar force field is used. For CN(-), the van der Waals ranges refined in our previous work yield hydration free energy between -72.0 and -77.2 kcal mol(-1), which is in excellent agreement with the experimental data. In addition to the cyanide ion, we also study the hydroxide ion to show that the method used here is readily applicable to similar systems. Hydration free energies are found to sensitively depend on the intermolecular interactions, while bonded interactions are less important, as expected. We also investigate in the present work the possibility of applying the multipolar force field in scoring trajectories generated using computationally inexpensive methods, which should be useful in broader parametrization studies with reduced computational resources, as scoring is much faster than the generation of the trajectories.
Lee, Myung Won; Meuwly, Markus
2013-12-14
The evaluation of hydration free energies is a sensitive test to assess force fields used in atomistic simulations. We showed recently that the vibrational relaxation times, 1D- and 2D-infrared spectroscopies for CN(-) in water can be quantitatively described from molecular dynamics (MD) simulations with multipolar force fields and slightly enlarged van der Waals radii for the C- and N-atoms. To validate such an approach, the present work investigates the solvation free energy of cyanide in water using MD simulations with accurate multipolar electrostatics. It is found that larger van der Waals radii are indeed necessary to obtain results close to the experimental values when a multipolar force field is used. For CN(-), the van der Waals ranges refined in our previous work yield hydration free energy between -72.0 and -77.2 kcal mol(-1), which is in excellent agreement with the experimental data. In addition to the cyanide ion, we also study the hydroxide ion to show that the method used here is readily applicable to similar systems. Hydration free energies are found to sensitively depend on the intermolecular interactions, while bonded interactions are less important, as expected. We also investigate in the present work the possibility of applying the multipolar force field in scoring trajectories generated using computationally inexpensive methods, which should be useful in broader parametrization studies with reduced computational resources, as scoring is much faster than the generation of the trajectories. PMID:24170171
Wijma, Hein J; Marrink, Siewert J; Janssen, Dick B
2014-07-28
Computational approaches could decrease the need for the laborious high-throughput experimental screening that is often required to improve enzymes by mutagenesis. Here, we report that using multiple short molecular dynamics (MD) simulations makes it possible to accurately model enantioselectivity for large numbers of enzyme-substrate combinations at low computational costs. We chose four different haloalkane dehalogenases as model systems because of the availability of a large set of experimental data on the enantioselective conversion of 45 different substrates. To model the enantioselectivity, we quantified the frequency of occurrence of catalytically productive conformations (near attack conformations) for pairs of enantiomers during MD simulations. We found that the angle of nucleophilic attack that leads to carbon-halogen bond cleavage was a critical variable that limited the occurrence of productive conformations; enantiomers for which this angle reached values close to 180° were preferentially converted. A cluster of 20-40 very short (10 ps) MD simulations allowed adequate conformational sampling and resulted in much better agreement to experimental enantioselectivities than single long MD simulations (22 ns), while the computational costs were 50-100 fold lower. With single long MD simulations, the dynamics of enzyme-substrate complexes remained confined to a conformational subspace that rarely changed significantly, whereas with multiple short MD simulations a larger diversity of conformations of enzyme-substrate complexes was observed. PMID:24916632
Lattice constant and substitutional composition of GeSn alloys grown by molecular beam epitaxy
NASA Astrophysics Data System (ADS)
Bhargava, Nupur; Coppinger, Matthew; Prakash Gupta, Jay; Wielunski, Leszek; Kolodzey, James
2013-07-01
Single crystal epitaxial Ge1-xSnx alloys with atomic fractions of tin up to x = 0.145 were grown by solid source molecular beam epitaxy on Ge (001) substrates. The Ge1-xSnx alloys formed high quality, coherent, strained layers at growth temperatures below 250 °C, as shown by high resolution X-ray diffraction. The amount of Sn that was on lattice sites, as determined by Rutherford backscattering spectrometry channeling, was found to be above 90% substitutional in all alloys. The degree of strain and the dependence of the effective unstrained bulk lattice constant of Ge1-xSnx alloys versus the composition of Sn have been determined.
Recent development and application of constant pH molecular dynamics
Chen, Wei; Morrow, Brian H.; Shi, Chuanyin; Shen, Jana K.
2014-01-01
Solution pH is a critical environmental factor for chemical and biological processes. Over the last decade, significant efforts have been made in the development of constant pH molecular dynamics (pHMD) techniques for gaining detailed insights into pH-coupled dynamical phenomena. In this article we review the advancement of this field in the past five years, placing a special emphasis on the development of the all-atom continuous pHMD technique. We discuss various applications, including the prediction of pKa shifts for proteins, nucleic acids and surfactant assemblies, elucidation of pH-dependent population shifts, protein-protein and protein-RNA binding, as well as the mechanisms of pH-dependent self-assembly and phase transitions of surfactants and peptides. We also discuss future directions for the further improvement of the pHMD techniques. PMID:25309035
Constant-pH Hybrid Nonequilibrium Molecular Dynamics-Monte Carlo Simulation Method.
Chen, Yunjie; Roux, Benoît
2015-08-11
A computational method is developed to carry out explicit solvent simulations of complex molecular systems under conditions of constant pH. In constant-pH simulations, preidentified ionizable sites are allowed to spontaneously protonate and deprotonate as a function of time in response to the environment and the imposed pH. The method, based on a hybrid scheme originally proposed by H. A. Stern (J. Chem. Phys. 2007, 126, 164112), consists of carrying out short nonequilibrium molecular dynamics (neMD) switching trajectories to generate physically plausible configurations with changed protonation states that are subsequently accepted or rejected according to a Metropolis Monte Carlo (MC) criterion. To ensure microscopic detailed balance arising from such nonequilibrium switches, the atomic momenta are altered according to the symmetric two-ends momentum reversal prescription. To achieve higher efficiency, the original neMD-MC scheme is separated into two steps, reducing the need for generating a large number of unproductive and costly nonequilibrium trajectories. In the first step, the protonation state of a site is randomly attributed via a Metropolis MC process on the basis of an intrinsic pKa; an attempted nonequilibrium switch is generated only if this change in protonation state is accepted. This hybrid two-step inherent pKa neMD-MC simulation method is tested with single amino acids in solution (Asp, Glu, and His) and then applied to turkey ovomucoid third domain and hen egg-white lysozyme. Because of the simple linear increase in the computational cost relative to the number of titratable sites, the present method is naturally able to treat extremely large systems. PMID:26300709
Molecular properties of alternative refrigerants derived from dielectric-constant measurements
Barao, M.T.; Castro, C.A.N. de; Mardolcar, U.V.
1997-03-01
A review of the current work in Lisbon on the measurement of the dielectric constant of the liquid phase of some environmentally acceptable refrigerants proposed as alternative replacements of the chlorofluorocarbons (CFCs), responsible for the destruction of the ozone layer, is presented. Measurements on HCFC 141b, HCFC 142b, HCFC 123, HFC 134a, HFC 152a, and HFC 32 samples of stated purities of 99.8 mass % or better were performed as a function of pressure and temperature, in the temperature range from 200 to 300 K and at pressures up to 20 MPa. The ratio of the capacitances of a cell filled with the sample and under vacuum was measured with a direct capacitance method. The dielectric-constant measurements have a repeatability of 0.003% and an accuracy of 0.1%. The theory developed by Vedam et al. based on the Eulerian Strain and the Kirkwood equation for the variation of the modified molar polarization with temperature and density were applied to obtain the dipole moments of the refrigerants in the liquid state, to obtain a physical insight of the molecular behavior, and to understand the equilibrium configuration of these liquids.
Sutter, Kiplangat; Truflandier, Lionel A; Autschbach, Jochen
2011-06-01
Solvent effects on J((195)Pt-(15)N) one-bond nuclear spin-spin coupling constants (J(PtN)) of cisplatin [cis-diamminedichloroplatinum(II)] and three cisplatin derivatives are investigated using a combination of density functional theory (DFT) based ab initio molecular dynamics (aiMD) and all-electron relativistic DFT NMR calculations employing the two-component relativistic zeroth-order regular approximation (ZORA). Good agreement with experiment is obtained when explicit solvent molecules are considered and when the computations are performed with a hybrid functional. Spin-orbit coupling causes only small effects on J(PtN) . Key factors contributing to the magnitude of coupling constants are elucidated, with the most significant being the presence of solvent as well as the quality of the density functional and basis set combination. The solvent effects are of the same magnitude as J(PtN) calculated for gas-phase geometries. However, the trends of J(PtN) among the complexes are already present in the gas phase. Results obtained with a continuum solvent model agree quite well with the aiMD results, provided that the Pt solvent-accessible radius is carefully chosen. The aiMD results support the existence of a partial hydrogen-bond-like inverse-hydration-type interaction affording a weak (1)J(Pt⋅⋅⋅H(w)) coupling between the complexes and the coordinating water molecule. PMID:21381179
NASA Astrophysics Data System (ADS)
Masunov, Artëm E.; Gangopadhyay, Shruba
2015-12-01
New method to eliminate the spin-contamination in broken symmetry density functional theory (BS DFT) calculations is introduced. Unlike conventional spin-purification correction, this method is based on canonical Natural Orbitals (NO) for each high/low spin coupled electron pair. We derive an expression to extract the energy of the pure singlet state given in terms of energy of BS DFT solution, the occupation number of the bonding NO, and the energy of the higher spin state built on these bonding and antibonding NOs (not self-consistent Kohn-Sham orbitals of the high spin state). Compared to the other spin-contamination correction schemes, spin-correction is applied to each correlated electron pair individually. We investigate two binuclear Mn(IV) molecular magnets using this pairwise correction. While one of the molecules is described by magnetic orbitals strongly localized on the metal centers, and spin gap is accurately predicted by Noodleman and Yamaguchi schemes, for the other one the gap is predicted poorly by these schemes due to strong delocalization of the magnetic orbitals onto the ligands. We show our new correction to yield more accurate results in both cases.
Unraveling HIV protease flaps dynamics by Constant pH Molecular Dynamics simulations.
Soares, Rosemberg O; Torres, Pedro H M; da Silva, Manuela L; Pascutti, Pedro G
2016-08-01
The active site of HIV protease (HIV-PR) is covered by two flaps. These flaps are known to be essential for the catalytic activity of the HIV-PR, but their exact conformations at the different stages of the enzymatic pathway remain subject to debate. Understanding the correct functional dynamics of the flaps might aid the development of new HIV-PR inhibitors. It is known that, the HIV-PR catalytic efficiency is pH-dependent, likely due to the influence of processes such as charge transfer and protonation/deprotonation of ionizable residues. Several Molecular Dynamics (MD) simulations have reported information about the HIV-PR flaps. However, in MD simulations the protonation of a residue is fixed and thus it is not possible to study the correlation between conformation and protonation state. To address this shortcoming, this work attempts to capture, through Constant pH Molecular Dynamics (CpHMD), the conformations of the apo, substrate-bound and inhibitor-bound HIV-PR, which differ drastically in their flap arrangements. The results show that the HIV-PR flaps conformations are defined by the protonation of the catalytic residues Asp25/Asp25' and that these residues are sensitive to pH changes. This study suggests that the catalytic aspartates can modulate the opening of the active site and substrate binding. PMID:27291071
2015-01-01
We present a new computational approach for constant pH simulations in explicit solvent based on the combination of the enveloping distribution sampling (EDS) and Hamiltonian replica exchange (HREX) methods. Unlike constant pH methods based on variable and continuous charge models, our method is based on discrete protonation states. EDS generates a hybrid Hamiltonian of different protonation states. A smoothness parameter s is used to control the heights of energy barriers of the hybrid-state energy landscape. A small s value facilitates state transitions by lowering energy barriers. Replica exchange between EDS potentials with different s values allows us to readily obtain a thermodynamically accurate ensemble of multiple protonation states with frequent state transitions. The analysis is performed with an ensemble obtained from an EDS Hamiltonian without smoothing, s = ∞, which strictly follows the minimum energy surface of the end states. The accuracy and efficiency of this method is tested on aspartic acid, lysine, and glutamic acid, which have two protonation states, a histidine with three states, a four-residue peptide with four states, and snake cardiotoxin with eight states. The pKa values estimated with the EDS-HREX method agree well with the experimental pKa values. The mean absolute errors of small benchmark systems range from 0.03 to 0.17 pKa units, and those of three titratable groups of snake cardiotoxin range from 0.2 to 1.6 pKa units. This study demonstrates that EDS-HREX is a potent theoretical framework, which gives the correct description of multiple protonation states and good calculated pKa values. PMID:25061443
NASA Astrophysics Data System (ADS)
Campbell, H. M.; Boardman, B. M.; DeVore, T. C.; Havey, D. K.
2012-12-01
This article describes an undergraduate laboratory exercise that uses optical spectroscopy to determine the magnitude and the uncertainty of the Boltzmann constant kb. The more accurate approach uses photoacoustic spectroscopy to measure the Doppler-broadened line profile of individual spectral lines of N2O to extract kb. Measurements and estimates of the uncertainties in the quantities needed to calculate kb from the line profiles are then used to estimate the uncertainty in kb. This experiment is unusual in that it uses advanced laser-based spectroscopy techniques to emphasize standard practices of uncertainty analysis. The core instrumentation is modular and relatively affordable; it requires a tunable single-mode laser, photoreceiver, optical cell, and vacuum pump. If this instrumentation is not available, an alternate approach can be performed which uses the intensity of each rotational transition of an infrared band to measure kb. Although there is more uncertainty using the alternate approach, low concentrations of CO2, DCl, or N2O give reasonable results for the magnitude of kb. Student assessment results indicate retention and mastery of the concept of combined measurement uncertainty.
NASA Astrophysics Data System (ADS)
Ansari, R.; Mirnezhad, M.; Sahmani, S.
2015-04-01
Molecular mechanics theory has been widely used to investigate the mechanical properties of nanostructures analytically. However, there is a limited number of research in which molecular mechanics model is utilized to predict the elastic properties of boron nitride nanotubes (BNNTs). In the current study, the mechanical properties of chiral single-walled BNNTs are predicted analytically based on an accurate molecular mechanics model. For this purpose, based upon the density functional theory (DFT) within the framework of the generalized gradient approximation (GGA), the exchange correlation of Perdew-Burke-Ernzerhof is adopted to evaluate force constants used in the molecular mechanics model. Afterwards, based on the principle of molecular mechanics, explicit expressions are given to calculate surface Young's modulus and Poisson's ratio of the single-walled BNNTs for different values of tube diameter and types of chirality. Moreover, the values of surface Young's modulus, Poisson's ratio and bending stiffness of boron nitride sheets are obtained via the DFT as byproducts. The results predicted by the present model are in reasonable agreement with those reported by other models in the literature.
Capturing molten globule state of α-lactalbumin through constant pH molecular dynamics simulations
NASA Astrophysics Data System (ADS)
Bhattacharjee, Nicholus; Rani, Pooja; Biswas, Parbati
2013-03-01
The recently developed methods of constant pH molecular dynamics directly captures the correlation between protonation and conformation to probe protein structure, function, and dynamics. In this work, we investigate the effect of pH on the conformational properties of the protein human α-lactalbumin. Constant pH simulations at both acidic and alkaline medium indicate the formation of the molten globule state, which is in accordance with the previous experimental observations (especially, in acidic medium). The size of the protein measured by its radius of gyration (RG) exhibits a marked increase in both acidic and alkaline medium, which matches with the corresponding experimentally observed value of RG found in the molten globule. The probability of native contacts is also considerably reduced at acidic and basic pH as compared to that of native structure crystallized at neutral pH. The mean fractal dimension D2 of the protein records a sharp increase in basic medium as compared to those in neutral and acidic solutions implying a significant pH induced conformational change. The mean square fluctuations of all residues of the entire protein are found to increase by several folds in both acidic and basic medium, which may be correlated with the normalized solvent accessibility of the residues indicating role of solvent accessible surface area on protein internal dynamics. The helices comprising the α-domain of the protein are moderately preserved in the acidic and alkaline pH. However, the β-sheet structures present in the β-domain are completely disrupted in both acidic as well as basic pH.
Perspective: Tipping the scales: Search for drifting constants from molecular spectra
Jansen, Paul; Bethlem, Hendrick L.; Ubachs, Wim
2014-01-07
Transitions in atoms and molecules provide an ideal test ground for constraining or detecting a possible variation of the fundamental constants of nature. In this perspective, we review molecular species that are of specific interest in the search for a drifting proton-to-electron mass ratio μ. In particular, we outline the procedures that are used to calculate the sensitivity coefficients for transitions in these molecules and discuss current searches. These methods have led to a rate of change in μ bounded to 6 × 10{sup −14}/yr from a laboratory experiment performed in the present epoch. On a cosmological time scale, the variation is limited to |Δμ/μ| < 10{sup −5} for look-back times of 10–12× 10{sup 9} years and to |Δμ/μ| < 10{sup −7} for look-back times of 7× 10{sup 9} years. The last result, obtained from high-redshift observation of methanol, translates into μ{sup .}/μ=(1.4±1.4)×10{sup −17}/yr if a linear rate of change is assumed.
Perspective: tipping the scales: search for drifting constants from molecular spectra.
Jansen, Paul; Bethlem, Hendrick L; Ubachs, Wim
2014-01-01
Transitions in atoms and molecules provide an ideal test ground for constraining or detecting a possible variation of the fundamental constants of nature. In this perspective, we review molecular species that are of specific interest in the search for a drifting proton-to-electron mass ratio μ. In particular, we outline the procedures that are used to calculate the sensitivity coefficients for transitions in these molecules and discuss current searches. These methods have led to a rate of change in μ bounded to 6 × 10(-14)/yr from a laboratory experiment performed in the present epoch. On a cosmological time scale, the variation is limited to ∣Δμ∕μ∣ < 10(-5) for look-back times of 10-12× 10(9) years and to ∣Δμ∕μ∣ < 10(-7) for look-back times of 7× 10(9) years. The last result, obtained from high-redshift observation of methanol, translates into μ̇/μ=(1.4±1.4)×10(-17)/yr if a linear rate of change is assumed. PMID:24410211
Costandy, Joseph; Michalis, Vasileios K; Tsimpanogiannis, Ioannis N; Stubos, Athanassios K; Economou, Ioannis G
2016-03-28
We introduce a simple correction to the calculation of the lattice constants of fully occupied structure sI methane or carbon dioxide pure hydrates that are obtained from classical molecular dynamics simulations using the TIP4PQ/2005 water force field. The obtained corrected lattice constants are subsequently used in order to obtain isobaric thermal expansion coefficients of the pure gas hydrates that exhibit a trend that is significantly closer to the experimental behavior than previously reported classical molecular dynamics studies. PMID:27036466
NASA Astrophysics Data System (ADS)
Grenev, I. V.; Gavrilov, V. Yu.
2014-01-01
Adsorption isotherms of molecular hydrogen are measured at 77 K in a series of AlPO alumophosphate zeolites with different microchannel sizes. The potential of the intermolecular interaction of H2 is calculated within the model of a cylindrical channel of variable size. Henry constants are calculated for this model for arbitrary orientations of the adsorbate molecules in microchannels. The experimental and calculated values of the Henry adsorption constant of H2 are compared at 77 K on AlPO zeolites. The constants of intermolecular interaction are determined for the H2-AlPO system.
Predicting Extreme pKa Shifts in Staphylococcal Nuclease Mutants with Constant pH Molecular Dynamics
Arthur, Evan J.; Yesselman, Joseph D.; Brooks, Charles L.
2011-01-01
Accurate computational methods of determining protein and nucleic acid pKa values are vital to understanding pH-dependent processes in biological systems. In this paper we use the recently developed method constant pH molecular dynamics (CPHMD) to explore the calculation of highly-perturbed pKa values in variants of staphylococcal nuclease (SNase). Simulations were performed using the replica exchange (REX) protocol for improved conformational sampling with eight temperature windows, and yielded converged proton populations in a total sampling time of 4 ns. Our REX-CPHMD simulations resulted in calculated pKa values with an average unsigned error (AUE) of 0.75 pK units for the acidic residues in Δ+PHS, a hyperstable variant of SNase. For highly pKa-perturbed SNase mutants with known crystal structures, our calculations yielded an AUE of 1.5 pK units and for those mutants based on modeled structures an AUE of 1.4 pK units was found. Although a systematic underestimate of pK shifts was observed in most of the cases for the highly perturbed pK mutants, correlations between conformational rearrangement and plasticity associated with the mutation and error in pKa prediction was not evident in the data. This study further extends the scope of electrostatic environments explored using the REX-CPHMD methodology and suggests it is a reliable tool for rapidly characterizing ionizable amino acids within proteins even when modeled structures are employed. PMID:22002886
NASA Astrophysics Data System (ADS)
Genova, Alessandro; Ceresoli, Davide; Pavanello, Michele
2016-06-01
In this work we achieve three milestones: (1) we present a subsystem DFT method capable of running ab-initio molecular dynamics simulations accurately and efficiently. (2) In order to rid the simulations of inter-molecular self-interaction error, we exploit the ability of semilocal frozen density embedding formulation of subsystem DFT to represent the total electron density as a sum of localized subsystem electron densities that are constrained to integrate to a preset, constant number of electrons; the success of the method relies on the fact that employed semilocal nonadditive kinetic energy functionals effectively cancel out errors in semilocal exchange-correlation potentials that are linked to static correlation effects and self-interaction. (3) We demonstrate this concept by simulating liquid water and solvated OH• radical. While the bulk of our simulations have been performed on a periodic box containing 64 independent water molecules for 52 ps, we also simulated a box containing 256 water molecules for 22 ps. The results show that, provided one employs an accurate nonadditive kinetic energy functional, the dynamics of liquid water and OH• radical are in semiquantitative agreement with experimental results or higher-level electronic structure calculations. Our assessments are based upon comparisons of radial and angular distribution functions as well as the diffusion coefficient of the liquid.
NASA Astrophysics Data System (ADS)
Meng, Qingyong; Chen, Jun; Zhang, Dong H.
2015-09-01
The ring polymer molecular dynamics (RPMD) calculations are performed to calculate rate constants for the title reaction on the recently constructed potential energy surface based on permutation invariant polynomial (PIP) neural-network (NN) fitting [J. Li et al., J. Chem. Phys. 142, 204302 (2015)]. By inspecting convergence, 16 beads are used in computing free-energy barriers at 300 K ≤ T ≤ 1000 K, while different numbers of beads are used for transmission coefficients. The present RPMD rates are in excellent agreement with quantum rates computed on the same potential energy surface, as well as with the experimental measurements, demonstrating further that the RPMD is capable of producing accurate rates for polyatomic chemical reactions even at rather low temperatures.
Nayak, Malaya K.; Chaudhuri, Rajat K.
2011-02-15
The spin-rotational Hamiltonian parameters A{sub ||} and A{sub perpendicular} for the BaF molecule are calculated using four-component relativistic spinors at the second-order many-body perturbation theory (MBPT) level via the Z-vector technique. The second-order MBPT is applied to assess the accuracy of the computed hyperfine-structure constants before studying the problem with the state-of-the-artcoupled cluster with single and double excitations (CCSD) method which is highly accurate but computationally more expensive than MBPT. The hyperfine-structure constants A and A{sub d} resulted from these calculations agree favorably well with experimental findings and with other correlated calculations. The convergence behavior of A and A{sub d} with respect to the number of active orbitals used in the perturbative calculations suggests that our estimated A and A{sub d} values should be accurate.
Fast and accurate modeling of molecular atomization energies with machine learning.
Rupp, Matthias; Tkatchenko, Alexandre; Müller, Klaus-Robert; von Lilienfeld, O Anatole
2012-02-01
We introduce a machine learning model to predict atomization energies of a diverse set of organic molecules, based on nuclear charges and atomic positions only. The problem of solving the molecular Schrödinger equation is mapped onto a nonlinear statistical regression problem of reduced complexity. Regression models are trained on and compared to atomization energies computed with hybrid density-functional theory. Cross validation over more than seven thousand organic molecules yields a mean absolute error of ∼10 kcal/mol. Applicability is demonstrated for the prediction of molecular atomization potential energy curves. PMID:22400967
Chocholousová, Jana; Feig, Michael
2006-04-30
Different integrator time steps in NVT and NVE simulations of protein and nucleic acid systems are tested with the GBMV (Generalized Born using Molecular Volume) and GBSW (Generalized Born with simple SWitching) methods. The simulation stability and energy conservation is investigated in relation to the agreement with the Poisson theory. It is found that very close agreement between generalized Born methods and the Poisson theory based on the commonly used sharp molecular surface definition results in energy drift and simulation artifacts in molecular dynamics simulation protocols with standard 2-fs time steps. New parameters are proposed for the GBMV method, which maintains very good agreement with the Poisson theory while providing energy conservation and stable simulations at time steps of 1 to 1.5 fs. PMID:16518883
NASA Astrophysics Data System (ADS)
Xin, Cui; Di-Yu, Zhang; Gao, Chen; Ji-Gen, Chen; Si-Liang, Zeng; Fu-Ming, Guo; Yu-Jun, Yang
2016-03-01
We demonstrate that the interference minima in the linear molecular harmonic spectra can be accurately predicted by a modified two-center model. Based on systematically investigating the interference minima in the linear molecular harmonic spectra by the strong-field approximation (SFA), it is found that the locations of the harmonic minima are related not only to the nuclear distance between the two main atoms contributing to the harmonic generation, but also to the symmetry of the molecular orbital. Therefore, we modify the initial phase difference between the double wave sources in the two-center model, and predict the harmonic minimum positions consistent with those simulated by SFA. Project supported by the National Basic Research Program of China (Grant No. 2013CB922200) and the National Natural Science Foundation of China (Grant Nos. 11274001, 11274141, 11304116, 11247024, and 11034003), and the Jilin Provincial Research Foundation for Basic Research, China (Grant Nos. 20130101012JC and 20140101168JC).
Schwörer, Magnus; Lorenzen, Konstantin; Mathias, Gerald; Tavan, Paul
2015-03-14
Recently, a novel approach to hybrid quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations has been suggested [Schwörer et al., J. Chem. Phys. 138, 244103 (2013)]. Here, the forces acting on the atoms are calculated by grid-based density functional theory (DFT) for a solute molecule and by a polarizable molecular mechanics (PMM) force field for a large solvent environment composed of several 10(3)-10(5) molecules as negative gradients of a DFT/PMM hybrid Hamiltonian. The electrostatic interactions are efficiently described by a hierarchical fast multipole method (FMM). Adopting recent progress of this FMM technique [Lorenzen et al., J. Chem. Theory Comput. 10, 3244 (2014)], which particularly entails a strictly linear scaling of the computational effort with the system size, and adapting this revised FMM approach to the computation of the interactions between the DFT and PMM fragments of a simulation system, here, we show how one can further enhance the efficiency and accuracy of such DFT/PMM-MD simulations. The resulting gain of total performance, as measured for alanine dipeptide (DFT) embedded in water (PMM) by the product of the gains in efficiency and accuracy, amounts to about one order of magnitude. We also demonstrate that the jointly parallelized implementation of the DFT and PMM-MD parts of the computation enables the efficient use of high-performance computing systems. The associated software is available online. PMID:25770527
Schwörer, Magnus; Lorenzen, Konstantin; Mathias, Gerald; Tavan, Paul
2015-03-14
Recently, a novel approach to hybrid quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations has been suggested [Schwörer et al., J. Chem. Phys. 138, 244103 (2013)]. Here, the forces acting on the atoms are calculated by grid-based density functional theory (DFT) for a solute molecule and by a polarizable molecular mechanics (PMM) force field for a large solvent environment composed of several 10{sup 3}-10{sup 5} molecules as negative gradients of a DFT/PMM hybrid Hamiltonian. The electrostatic interactions are efficiently described by a hierarchical fast multipole method (FMM). Adopting recent progress of this FMM technique [Lorenzen et al., J. Chem. Theory Comput. 10, 3244 (2014)], which particularly entails a strictly linear scaling of the computational effort with the system size, and adapting this revised FMM approach to the computation of the interactions between the DFT and PMM fragments of a simulation system, here, we show how one can further enhance the efficiency and accuracy of such DFT/PMM-MD simulations. The resulting gain of total performance, as measured for alanine dipeptide (DFT) embedded in water (PMM) by the product of the gains in efficiency and accuracy, amounts to about one order of magnitude. We also demonstrate that the jointly parallelized implementation of the DFT and PMM-MD parts of the computation enables the efficient use of high-performance computing systems. The associated software is available online.
NASA Astrophysics Data System (ADS)
Schwörer, Magnus; Lorenzen, Konstantin; Mathias, Gerald; Tavan, Paul
2015-03-01
Recently, a novel approach to hybrid quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations has been suggested [Schwörer et al., J. Chem. Phys. 138, 244103 (2013)]. Here, the forces acting on the atoms are calculated by grid-based density functional theory (DFT) for a solute molecule and by a polarizable molecular mechanics (PMM) force field for a large solvent environment composed of several 103-105 molecules as negative gradients of a DFT/PMM hybrid Hamiltonian. The electrostatic interactions are efficiently described by a hierarchical fast multipole method (FMM). Adopting recent progress of this FMM technique [Lorenzen et al., J. Chem. Theory Comput. 10, 3244 (2014)], which particularly entails a strictly linear scaling of the computational effort with the system size, and adapting this revised FMM approach to the computation of the interactions between the DFT and PMM fragments of a simulation system, here, we show how one can further enhance the efficiency and accuracy of such DFT/PMM-MD simulations. The resulting gain of total performance, as measured for alanine dipeptide (DFT) embedded in water (PMM) by the product of the gains in efficiency and accuracy, amounts to about one order of magnitude. We also demonstrate that the jointly parallelized implementation of the DFT and PMM-MD parts of the computation enables the efficient use of high-performance computing systems. The associated software is available online.
Machuqueiro, Miguel; Baptista, António M
2011-12-01
In this study, we investigate two factors that can hinder the performance of constant-pH molecular dynamics methods in predicting protein pK(a) values, using hen egg white lysozyme as a test system. The first factor is related to the molecular definition and pK(a) value of model compounds in the Poisson-Boltzmann framework. We address this by defining the model compound as a molecular fragment with an associated pK(a) value that is calibrated against experimental data, which results in a decrease of 0.12 units in pK(a) errors. The second addressed factor is the possibility that detrimental structural distortions are being introduced in the simulations by the underlying molecular mechanics force field. This issue is investigated by analyzing how the gradual structural rearrangements affect the predicted pK(a) values. The two GROMOS force fields studied here (43A1 and 53A6) yield good pK(a) predictions, although a time-dependent performance is observed: 43A1 performs better after a few nanoseconds of structural reorganization (pK(a) errors of ~0.45), while 53A6 gives the best prediction right at the first nanosecond (pK(a) errors of 0.42). These results suggest that the good performance of constant-pH molecular dynamics methods could be further improved if these force field limitations were overcome. PMID:22072522
Huang, Xinchuan; Valeev, Edward F; Lee, Timothy J
2010-12-28
One-particle basis set extrapolation is compared with one of the new R12 methods for computing highly accurate quartic force fields (QFFs) and spectroscopic data, including molecular structures, rotational constants, and vibrational frequencies for the H(2)O, N(2)H(+), NO(2)(+), and C(2)H(2) molecules. In general, agreement between the spectroscopic data computed from the best R12 and basis set extrapolation methods is very good with the exception of a few parameters for N(2)H(+) where it is concluded that basis set extrapolation is still preferred. The differences for H(2)O and NO(2)(+) are small and it is concluded that the QFFs from both approaches are more or less equivalent in accuracy. For C(2)H(2), however, a known one-particle basis set deficiency for C-C multiple bonds significantly degrades the quality of results obtained from basis set extrapolation and in this case the R12 approach is clearly preferred over one-particle basis set extrapolation. The R12 approach used in the present study was modified in order to obtain high precision electronic energies, which are needed when computing a QFF. We also investigated including core-correlation explicitly in the R12 calculations, but conclude that current approaches are lacking. Hence core-correlation is computed as a correction using conventional methods. Considering the results for all four molecules, it is concluded that R12 methods will soon replace basis set extrapolation approaches for high accuracy electronic structure applications such as computing QFFs and spectroscopic data for comparison to high-resolution laboratory or astronomical observations, provided one uses a robust R12 method as we have done here. The specific R12 method used in the present study, CCSD(T)(R12), incorporated a reformulation of one intermediate matrix in order to attain machine precision in the electronic energies. Final QFFs for N(2)H(+) and NO(2)(+) were computed, including basis set extrapolation, core-correlation, scalar
NASA Astrophysics Data System (ADS)
Morishita, Tetsuya
2001-09-01
Pressure-induced phase transitions in liquid phosphorus have been studied by constant-pressure first-principles molecular dynamics simulations. By compressing a low-pressure liquid which consists of the tetrahedral P4 molecules, a structural phase transition from the molecular to polymeric liquid (a high-pressure phase) observed in the recent experiment by Katayama et al. [Nature (London) 403, 170 (2000)] was successfully realized. It is found that this transition is caused by a breakup of the tetrahedral molecules with large volume contraction. The same transition is also realized by heating. This indicates that only the polymeric liquid can stably exist at high temperature.
NASA Astrophysics Data System (ADS)
Flores-Ruiz, Hugo M.; Naumis, Gerardo G.
2009-10-01
Using molecular dynamics at constant pressure, the relationship between the excess of low frequency vibrational modes (known as the boson peak) and the glass transition is investigated for a truncated Lennard-Jones potential. It is observed that the quadratic mean displacement is enhanced by such modes, as predicted using a harmonic Hamiltonian for metastable states. As a result, glasses loose mechanical stability at lower temperatures than the corresponding crystal, since the Lindemann criteria are observed, as is also deduced from density functional theory. Finally, we found that the average force and elastic constant are reduced in the glass due to such excess of modes. The ratio between average elastic constants can be approximated using the 2/3 rule between melting and glass transition temperatures.
Molecular Detection of Foodborne Pathogens: A Rapid and Accurate Answer to Food Safety.
Mangal, Manisha; Bansal, Sangita; Sharma, Satish K; Gupta, Ram K
2016-07-01
Food safety is a global health concern. For the prevention and recognition of problems related to health and safety, detection of foodborne pathogen is of utmost importance at all levels of food production chain. For several decades, a lot of research has been targeted at the development of rapid methodology as reducing the time needed to complete pathogen detection tests has been the primary goal of food microbiologists. With the result, food microbiology laboratories now have a wide array of detection methods and automated technologies such as enzyme immunoassay, polymerase chain reaction, and microarrays, which can cut test times considerably. Nucleic acid amplification strategies and advances in amplicon detection methodologies have been the key factors in the progress of molecular microbiology. A comprehensive literature survey has been carried out to give an overview in the field of foodborne pathogen detection. In this paper, we describe the conventional methods, as well as recent developments in food pathogen detection, identification, and quantification, with a major emphasis on molecular detection methods. PMID:25830555
Accurate decay-constant ratios fB*/fB and fBs*/fBs from Borel QCD sum rules
NASA Astrophysics Data System (ADS)
Lucha, Wolfgang; Melikhov, Dmitri; Simula, Silvano
2015-06-01
We present our analysis of the decay constants of the beauty vector mesons B* and Bs* within the framework of dispersive sum rules for the two-point correlator of vector currents in QCD. While the decay constants of the vector mesons fB* and fBs* —similar to the decay constants of the pseudoscalar mesons fB and fBs—individuallyhave large uncertainties induced by theory parameters not known with a satisfactory precision, these uncertainties almost entirely cancel out in the ratios of vector over pseudoscalar decay constants. These ratios, thus, may be predicted with very high accuracy due to the good control over the systematic uncertainties of the decay constants gained upon application of our hadron-parameter extraction algorithm. Our final results read fB*/fB=0.944 ±0.01 1OPE±0.01 8syst and fBs*/fB s=0.947 ±0.02 3OPE±0.02 0syst . Thus, both fB*/fB and fBs*/fBs are less than unity at 2.5 σ and 2 σ level, respectively.
A simple and accurate algorithm for path integral molecular dynamics with the Langevin thermostat.
Liu, Jian; Li, Dezhang; Liu, Xinzijian
2016-07-14
We introduce a novel simple algorithm for thermostatting path integral molecular dynamics (PIMD) with the Langevin equation. The staging transformation of path integral beads is employed for demonstration. The optimum friction coefficients for the staging modes in the free particle limit are used for all systems. In comparison to the path integral Langevin equation thermostat, the new algorithm exploits a different order of splitting for the phase space propagator associated to the Langevin equation. While the error analysis is made for both algorithms, they are also employed in the PIMD simulations of three realistic systems (the H2O molecule, liquid para-hydrogen, and liquid water) for comparison. It is shown that the new thermostat increases the time interval of PIMD by a factor of 4-6 or more for achieving the same accuracy. In addition, the supplementary material shows the error analysis made for the algorithms when the normal-mode transformation of path integral beads is used. PMID:27421393
Hepburn, I; Chen, W; De Schutter, E
2016-08-01
Spatial stochastic molecular simulations in biology are limited by the intense computation required to track molecules in space either in a discrete time or discrete space framework, which has led to the development of parallel methods that can take advantage of the power of modern supercomputers in recent years. We systematically test suggested components of stochastic reaction-diffusion operator splitting in the literature and discuss their effects on accuracy. We introduce an operator splitting implementation for irregular meshes that enhances accuracy with minimal performance cost. We test a range of models in small-scale MPI simulations from simple diffusion models to realistic biological models and find that multi-dimensional geometry partitioning is an important consideration for optimum performance. We demonstrate performance gains of 1-3 orders of magnitude in the parallel implementation, with peak performance strongly dependent on model specification. PMID:27497550
NASA Astrophysics Data System (ADS)
Hepburn, I.; Chen, W.; De Schutter, E.
2016-08-01
Spatial stochastic molecular simulations in biology are limited by the intense computation required to track molecules in space either in a discrete time or discrete space framework, which has led to the development of parallel methods that can take advantage of the power of modern supercomputers in recent years. We systematically test suggested components of stochastic reaction-diffusion operator splitting in the literature and discuss their effects on accuracy. We introduce an operator splitting implementation for irregular meshes that enhances accuracy with minimal performance cost. We test a range of models in small-scale MPI simulations from simple diffusion models to realistic biological models and find that multi-dimensional geometry partitioning is an important consideration for optimum performance. We demonstrate performance gains of 1-3 orders of magnitude in the parallel implementation, with peak performance strongly dependent on model specification.
NASA Technical Reports Server (NTRS)
Boughner, Robert E.
1986-01-01
A method for calculating the photodissociation rates needed for photochemical modeling of the stratosphere, which includes the effects of molecular scattering, is described. The procedure is based on Sokolov's method of averaging functional correction. The radiation model and approximations used to calculate the radiation field are examined. The approximated diffuse fields and photolysis rates are compared with exact data. It is observed that the approximate solutions differ from the exact result by 10 percent or less at altitudes above 15 km; the photolysis rates differ from the exact rates by less than 5 percent for altitudes above 10 km and all zenith angles, and by less than 1 percent for altitudes above 15 km.
A simple and accurate algorithm for path integral molecular dynamics with the Langevin thermostat
NASA Astrophysics Data System (ADS)
Liu, Jian; Li, Dezhang; Liu, Xinzijian
2016-07-01
We introduce a novel simple algorithm for thermostatting path integral molecular dynamics (PIMD) with the Langevin equation. The staging transformation of path integral beads is employed for demonstration. The optimum friction coefficients for the staging modes in the free particle limit are used for all systems. In comparison to the path integral Langevin equation thermostat, the new algorithm exploits a different order of splitting for the phase space propagator associated to the Langevin equation. While the error analysis is made for both algorithms, they are also employed in the PIMD simulations of three realistic systems (the H2O molecule, liquid para-hydrogen, and liquid water) for comparison. It is shown that the new thermostat increases the time interval of PIMD by a factor of 4-6 or more for achieving the same accuracy. In addition, the supplementary material shows the error analysis made for the algorithms when the normal-mode transformation of path integral beads is used.
Towards More Accurate Measurements of the Ionization Energy of Molecular Hydrogen
NASA Astrophysics Data System (ADS)
Sprecher, D.; Beyer, M.; Liu, J.; Merkt, F.; Salumbides, E.; Eikema, K. S. E.; Ubachs, W.; Jungen, Ch.
2013-06-01
With two electrons and two protons, molecular hydrogen is the simplest molecule displaying all features of a chemical bond. H_2 is therefore a fundamental system for testing molecular quantum mechanics and quantum electrodynamics in molecules. The test can be performed by comparing measured and calculated intervals between different rovibronic states of H_2. Two further quantities that can be used for this test are the dissociation and ionization energies of H_2, and considerable efforts have been invested over more than 80 years to improve the precision and accuracy of experimental and theoretical determination of these two quantities. The current status of the comparison is that the theoretical and experimental values of the ionization and dissociation energies of H_2 agree within the combined uncertainty of 30 MHz (see also). The factors currently limiting the precision of the experimental determination will be discussed and the strategies that are being implemented towards overcoming these limitations will be presented. A long-term goal is to achieve a precision of better than 15 kHz, which is the ultimate limit imposed on the accuracy of the theoretical determination by the current uncertainty of the proton-to-electron mass ratio. E. J. Salumbides, G. D. Dickenson, T. I. Ivanov and W. Ubachs, {Phys. Rev. Lett.} 107 (4), 043005 (2011). K. Piszczatowski, G. Lach, M. Przybytek, J. Komasa, K. Pachuckiand and B. Jeziorski, {J. Chem. Theory Comput.} 5 (11), 3039 (2009). J. Liu, E. J. Salumbides, U. Hollenstein, J. C. J. Koelemeij, K. S. E. Eikema, W. Ubachs and F. Merkt, {J. Chem. Phys.} 130 (17), 174306 (2009). D. Sprecher, Ch. Jungen, W. Ubachs and F. Merkt, {Faraday Discuss.} 150, 51 (2011).
Accurate description of phase diagram of clathrate hydrates at the molecular level
NASA Astrophysics Data System (ADS)
Belosludov, Rodion V.; Subbotin, Oleg S.; Mizuseki, Hiroshi; Kawazoe, Yoshiyuki; Belosludov, Vladimir R.
2009-12-01
In order to accurately estimate the thermodynamic properties of hydrogen clathrate hydrates, we developed a method based on the solid solution theory of van der Waals and Platteeuw. This model allows one to take into account the influence of guest molecules on the host lattice and guest-guest interactions—especially when more than one guest molecule occupies a cage. The free energies, equations of state, and chemical potentials of hydrogen and mixed propane-hydrogen clathrate hydrates of cubic structure II with different cage fillings have been estimated using this approach. Moreover, the proposed theory has been used for construction p -T phase diagrams of hydrogen hydrate and mixed hydrogen-propane hydrates in a wide range of pressures and temperatures. For the systems with well defined interactions the calculated curves of "guest gas-hydrate-ice Ih" equilibrium agree with the available experimental data. We also believe that the present model allows one not only to calculate the hydrogen storage ability of known hydrogen hydrate but also predict this value for structures that have not yet been realized by experiment.
Microbial transformation rate constants for a series of phenols were correlated with a property of the substituents, van der Waal's radius. Transformation products were the corresponding catecols, with the exception of p-hydroxybenzoic acid, the product of p-acetylphenol. A diffe...
Estimation of Henry's Law Constant for a Diverse Set of Organic Compounds from Molecular Structure
The SPARC (SPARC Performs Automated Reasoning in Chemistry) vapor pressure and activity coefficient models were coupled to estimate Henry’s Law Constant (HLC) in water and in hexadecane for a wide range of non-polar and polar organic compounds without modification or additional p...
Accurate Photodissociation in UV and X-ray Irradiated Molecular Gas
NASA Astrophysics Data System (ADS)
Stancil, Phillip C.; Gay, C. D.; Cieszewski, R. M.; el-Qadi, W.; Kuri, A.; Miyake, S.; Abel, N.; Porter, R. L.; Shaw, G.; Ferland, G. J.; van Hoof, P. A. M.
2011-05-01
Molecules are primarily destroyed in diffuse and translucent regions, in protoplanetary disks, in cool stellar atmospheres, in photodissociation regions, and in x-ray dominated regions via photodissociation (PD) due to the incident radiation field. The majority of astrochemical/spectral modeling codes available today use pre-computed exponentially-attenuated photorates based on dust scattering/absorption for an ``average" interstellar cloud. Since there is clearly a large scatter in the dust properties and local radiation field for various environments in the Galaxy and beyond, the adoption of such pre-computed photorates can lead to considerable errors in predicted abundances. To improve current modeling capabilities, we are computing new rovibrationally-resolved PD cross sections for H_2, HD, HeH+, NH, C_2, CN, and CS and implementing the cross sections in the spectral simulation code Cloudy for explicit computation of local photorates. We present model results using the new photodissociation cross sections for a variety of environments emphasizing differences in total and state-specific molecular column densities. This work was partially supported by NASA grants NNG06GJ11G and HST-AR-11776.01-A, NSF grant AST-0607733, and the PRODEX Programme of ESA.
NASA Technical Reports Server (NTRS)
Dembosky, Stanley K.; Sancaktar, Erol
1985-01-01
The bonded shear creep and constant strain rate behaviors of zero, one, and three percent endcapped thermoplastic polyimidesulfone adhesive were examined at room and elevated temperatures. Endcapping was accomplished by the addition of phthalic anhydrides. The primary objective was to determine the effects of molecular weight on the mechanical properties of the adhesive. Viscoelastic and nonlinear elastic constitutive equations were utilized to model the adhesive. Ludwik's and Crochet's relations were used to describe the experimental failure data. The effects of molecular weight changes on the above mentioned mechanical behavior were assessed. The viscoelastic Chase-Goldsmith and elastic nonlinear relations gave a good fit to the experimental stress strain behavior. Crochet's relations based on Maxwell and Chase-Goldsmith models were fit to delayed failure data. Ludwik's equations revealed negligible rate dependence. Ultimate stress levels and the safe levels for creep stresses were found to decrease as molecular weight was reduced.
NASA Astrophysics Data System (ADS)
Morishita, Tetsuya
2001-12-01
Constant-pressure first-principles molecular dynamics simulations have been carried out to study structural phase transitions of liquid black phosphorus. By compressing the tetrahedral molecular liquid (a low-pressure phase), a structural phase transition from the molecular to polymeric liquid (a high-pressure phase) was successfully realized just as observed in the recent experiment by Katayama et al. [Nature 170 (2000) 403]. Structural properties in the polymeric liquid were investigated and it is found that the covalent p-state bonds are dominant within the first nearest neighbors of each atom. However, further compression of the polymeric liquid shows that the covalent bonding is weakened as pressure is increased. As a result, liquid phosphorus becomes similar to the simple liquid in which atoms form a close-packed structure at very high pressure.
NASA Astrophysics Data System (ADS)
Sahu, Nityananda; Gadre, Shridhar R.
2015-01-01
In spite of the recent advents in parallel algorithms and computer hardware, high-level calculation of vibrational spectra of large molecules is still an uphill task. To overcome this, significant effort has been devoted to the development of new algorithms based on fragmentation methods. The present work provides the details of an efficient and accurate procedure for computing the vibrational spectra of large clusters employing molecular tailoring approach (MTA). The errors in the Hessian matrix elements and dipole derivatives arising due to the approximation nature of MTA are reduced by grafting the corrections from a smaller basis set. The algorithm has been tested out for obtaining vibrational spectra of neutral and charged water clusters at Møller-Plesset second order level of theory, and benchmarking them against the respective full calculation (FC) and/or experimental results. For (H2O)16 clusters, the estimated vibrational frequencies are found to differ by a maximum of 2 cm-1 with reference to the corresponding FC values. Unlike the FC, the MTA-based calculations including grafting procedure can be performed on a limited hardware, yet take a fraction of the FC time. The present methodology, thus, opens a possibility of the accurate estimation of the vibrational spectra of large molecular systems, which is otherwise impossible or formidable.
Sahu, Nityananda; Gadre, Shridhar R
2015-01-01
In spite of the recent advents in parallel algorithms and computer hardware, high-level calculation of vibrational spectra of large molecules is still an uphill task. To overcome this, significant effort has been devoted to the development of new algorithms based on fragmentation methods. The present work provides the details of an efficient and accurate procedure for computing the vibrational spectra of large clusters employing molecular tailoring approach (MTA). The errors in the Hessian matrix elements and dipole derivatives arising due to the approximation nature of MTA are reduced by grafting the corrections from a smaller basis set. The algorithm has been tested out for obtaining vibrational spectra of neutral and charged water clusters at Møller-Plesset second order level of theory, and benchmarking them against the respective full calculation (FC) and/or experimental results. For (H2O)16 clusters, the estimated vibrational frequencies are found to differ by a maximum of 2 cm(-1) with reference to the corresponding FC values. Unlike the FC, the MTA-based calculations including grafting procedure can be performed on a limited hardware, yet take a fraction of the FC time. The present methodology, thus, opens a possibility of the accurate estimation of the vibrational spectra of large molecular systems, which is otherwise impossible or formidable. PMID:25573553
NASA Astrophysics Data System (ADS)
Luo, Ye; Sorella, Sandro
2014-03-01
We introduce a general and efficient method for the calculation of vibrational frequencies of electronic systems, ranging from molecules to solids. By performing damped molecular dynamics with ab initio forces, we show that quantum vibrational frequencies can be evaluated by diagonalizing the time averaged position-position or force-force correlation matrices, although the ionic motion is treated on the classical level within the Born-Oppenheimer approximation. The novelty of our approach is to evaluate atomic forces with QMC by means of a highly accurate and correlated variational wave function which is optimized simultaneously during the dynamics. QMC is an accurate and promising many-body technique for electronic structure calculation thanks to massively parallel computers. However, since infinite statistics is not feasible, property evaluation may be affected by large noise that is difficult to harness. Our approach controls the QMC stochastic bias systematically and gives very accurate results with moderate computational effort, namely even with noisy forces. We prove the accuracy and efficiency of our method on the water monomer[A. Zen et al., JCTC 9 (2013) 4332] and dimer. We are currently working on the challenging problem of simulating liquid water at ambient conditions.
NASA Astrophysics Data System (ADS)
Álvarez-Bajo, O.; Sánchez-Castellanos, M.; Amezcua-Eccius, C. A.; Lemus, R.
2006-06-01
A connection between the unitary group approach U ( ν + 1) and the traditional description in configuration space of vibrational excitations is proposed. Local operators bˆi†(b) satisfying the su (2) commutation relations are used to establish approximate algebraic expansions of the local coordinates and momenta. The use of the proposed relations allows to obtain an algebraic representation of traditional Hamiltonians in terms of the U ( ν + 1) model. This approach provides in natural form the connection between the spectroscopic parameters and force constants. Using the linear expansion of the coordinates in terms of the bˆi†(b) operators, an approach to study local dipole transition intensities based on traditional descriptions is proposed. A closed general analytical expression for the local dipole operators is obtained. The analysis of the stretching vibrational excitations of arsine is taken as an example for the determination of both force constants and the description of dipole transition intensities.
NASA Astrophysics Data System (ADS)
Mohapatra, Himansu; Eckhardt, Craig J.
2007-03-01
Polymorphism is the property of a compound to crystallize in two or more crystalline phases containing different arrangements and/or conformations of the molecules in the crystal lattice. The Phenomenon of polymorphism is a major issue in the pharmaceutical industry especially in relation to drug uptake in the body, tablet processing and growth. This has led to considerable interest in predicting and understanding properties of drug polymorphs, and more recently the mechanical properties of the polymorphs. In this work, Brillouin scattering is used to probe the acoustic phonons of the monoclinic (P21/c) polymorph of the drug, carbamazepine (CBZ). By sampling a variety of acoustic phonons, the complete elastic constant tensor has been determined for this CBZ polymorph. The observed trend in the elastic constants: C11< C22˜C33 is qualitatively associated with the crystal growth pattern seen in CBZ. Investigation into the anisotropy of the intermolecular interactions has been investigated further by calculation of linear compressibilities.
Safaei, B; Naseradinmousavi, P; Rahmani, A
2016-04-01
In the present paper, an analytical solution based on a molecular mechanics model is developed to evaluate the elastic critical axial buckling strain of chiral multi-walled carbon nanotubes (MWCNTs). To this end, the total potential energy of the system is calculated with the consideration of the both bond stretching and bond angular variations. Density functional theory (DFT) in the form of generalized gradient approximation (GGA) is implemented to evaluate force constants used in the molecular mechanics model. After that, based on the principle of molecular mechanics, explicit expressions are proposed to obtain elastic surface Young's modulus and Poisson's ratio of the single-walled carbon nanotubes corresponding to different types of chirality. Selected numerical results are presented to indicate the influence of the type of chirality, tube diameter, and number of tube walls in detailed. An excellent agreement is found between the present numerical results and those found in the literature which confirms the validity as well as the accuracy of the present closed-form solution. It is found that the value of critical axial buckling strain exhibit significant dependency on the type of chirality and number of tube walls. PMID:26930445
Deridder, Sander; Desmet, Gert
2012-02-01
Using computational fluid dynamics (CFD), the effective B-term diffusion constant γ(eff) has been calculated for four different random sphere packings with different particle size distributions and packing geometries. Both fully porous and porous-shell sphere packings are considered. The obtained γ(eff)-values have subsequently been used to determine the value of the three-point geometrical constant (ζ₂) appearing in the 2nd-order accurate effective medium theory expression for γ(eff). It was found that, whereas the 1st-order accurate effective medium theory expression is accurate to within 5% over most part of the retention factor range, the 2nd-order accurate expression is accurate to within 1% when calculated with the best-fit ζ₂-value. Depending on the exact microscopic geometry, the best-fit ζ₂-values typically lie in the range of 0.20-0.30, holding over the entire range of intra-particle diffusion coefficients typically encountered for small molecules (0.1 ≤ D(pz)/D(m) ≤ 0.5). These values are in agreement with the ζ₂-value proposed by Thovert et al. for the random packing they considered. PMID:22236565
NASA Astrophysics Data System (ADS)
Desforges, Jean; Deschamps, Clément; Gauvin, Serge
2015-08-01
The determination of the complex refractive index of thin films usually requires the highest accuracy. In this paper, we report on a new and accurate method based on a spectral rectifying process of a single transmittance curve. The agreements with simulated and real experimental data show the helpfulness of the method. The case of materials having arbitrary absorption bands at midpoint in spectral range, such as pigments in guest-host polymers, is also encompassed by this method.
Huang Xinchuan; Fortenberry, Ryan C.; Lee, Timothy J.
2013-05-10
Very recently, molecular rotational transitions observed in the photon-dominated region of the Horsehead nebula have been attributed to l-C{sub 3}H{sup +}. In an effort to corroborate this finding, we employed state-of-the-art and proven high-accuracy quantum chemical techniques to compute spectroscopic constants for this cation and its isotopologues. Even though the B rotational constant from the fit of the observed spectrum and our computations agree to within 20 MHz, a typical level of accuracy, the D rotational constant differs by more than 40%, while the H rotational constant differs by three orders of magnitude. With the likely errors in the rotational transition energies resulting from this difference in D on the order of 1 MHz for the lowest observed transition (J = 4 {yields} 3) and growing as J increases, the assignment of the observed rotational lines from the Horsehead nebula to l-C{sub 3}H{sup +} is questionable.
NASA Astrophysics Data System (ADS)
Huang, Xinchuan; Fortenberry, Ryan C.; Lee, Timothy J.
2013-05-01
Very recently, molecular rotational transitions observed in the photon-dominated region of the Horsehead nebula have been attributed to l-C3H+. In an effort to corroborate this finding, we employed state-of-the-art and proven high-accuracy quantum chemical techniques to compute spectroscopic constants for this cation and its isotopologues. Even though the B rotational constant from the fit of the observed spectrum and our computations agree to within 20 MHz, a typical level of accuracy, the D rotational constant differs by more than 40%, while the H rotational constant differs by three orders of magnitude. With the likely errors in the rotational transition energies resulting from this difference in D on the order of 1 MHz for the lowest observed transition (J = 4 → 3) and growing as J increases, the assignment of the observed rotational lines from the Horsehead nebula to l-C3H+ is questionable.
NASA Technical Reports Server (NTRS)
Huang, Xinchuan; Fortenberry, Ryan Clifton; Lee, Timothy J.
2013-01-01
Very recently, molecular rotational transitions observed in the photon-dominated region of the Horsehead nebula have been attributed to l-C3H+. In an effort to corroborate this finding, we employed state-of-the art and proven high-accuracy quantum chemical techniques to compute spectroscopic constants for this cation and its isotopologues. Even though the B rotational constant from the fit of the observed spectrum and our computations agree to within 20 MHz, a typical level of accuracy, the D rotational constant differs by more than 40%, while the H rotational constant differs by three orders of magnitude. With the likely errors in the rotational transition energies resulting from this difference in D on the order of 1 MHz for the lowest observed transition (J = 4 yields 3) and growing as J increases, the assignment of the observed rotational lines from the Horsehead nebula to l-C3H+ is questionable.
2015-01-01
By utilizing Graphics Processing Units, we show that constant pH molecular dynamics simulations (CpHMD) run in Generalized Born (GB) implicit solvent for long time scales can yield poor pKa predictions as a result of sampling unrealistic conformations. To address this shortcoming, we present a method for performing constant pH molecular dynamics simulations (CpHMD) in explicit solvent using a discrete protonation state model. The method involves standard molecular dynamics (MD) being propagated in explicit solvent followed by protonation state changes being attempted in GB implicit solvent at fixed intervals. Replica exchange along the pH-dimension (pH-REMD) helps to obtain acceptable titration behavior with the proposed method. We analyzed the effects of various parameters and settings on the titration behavior of CpHMD and pH-REMD in explicit solvent, including the size of the simulation unit cell and the length of the relaxation dynamics following protonation state changes. We tested the method with the amino acid model compounds, a small pentapeptide with two titratable sites, and hen egg white lysozyme (HEWL). The proposed method yields superior predicted pKa values for HEWL over hundreds of nanoseconds of simulation relative to corresponding predicted values from simulations run in implicit solvent. PMID:24803862
Mackie, Cameron J; Candian, Alessandra; Huang, Xinchuan; Lee, Timothy J; Tielens, Alexander G G M
2015-06-28
A full derivation of the analytic transformation of the quadratic, cubic, and quartic force constants from normal coordinates to Cartesian coordinates is given. Previous attempts at this transformation have resulted in non-linear transformations; however, for the first time, a simple linear transformation is presented here. Two different approaches have been formulated and implemented, one of which does not require prior knowledge of the translation-rotation eigenvectors from diagonalization of the Hessian matrix. The validity of this method is tested using two molecules H2O and c-C3H2D(+). PMID:26133410
The protective effect of a constant magnetic field. [reduction of molecular cell pathology
NASA Technical Reports Server (NTRS)
Sosunov, A. V.; Tripuzov, A. N.
1974-01-01
The protective effect of a constant magnetic field sharply reduced spontaneous lysis of E. coli cells when subjected to ultraviolet radiation. A protective effect of a CMF was found in a study of tissue cultures of normally growing cells (kidney epithelium) and cancer cells (cells from a cancer of the larynx). The protective effect of a CMF is also seen in a combined exposure of tissue cultures to X-rays and CMF energy (strength of the CMF was 2000 oersteds with a gradient of 500 oersteds/cm). The data obtained are of interest to experimental oncology (development of new methods of treating malignant tumors).
Dunn, Nicholas J. H.; Noid, W. G.
2015-12-28
The present work investigates the capability of bottom-up coarse-graining (CG) methods for accurately modeling both structural and thermodynamic properties of all-atom (AA) models for molecular liquids. In particular, we consider 1, 2, and 3-site CG models for heptane, as well as 1 and 3-site CG models for toluene. For each model, we employ the multiscale coarse-graining method to determine interaction potentials that optimally approximate the configuration dependence of the many-body potential of mean force (PMF). We employ a previously developed “pressure-matching” variational principle to determine a volume-dependent contribution to the potential, U{sub V}(V), that approximates the volume-dependence of the PMF. We demonstrate that the resulting CG models describe AA density fluctuations with qualitative, but not quantitative, accuracy. Accordingly, we develop a self-consistent approach for further optimizing U{sub V}, such that the CG models accurately reproduce the equilibrium density, compressibility, and average pressure of the AA models, although the CG models still significantly underestimate the atomic pressure fluctuations. Additionally, by comparing this array of models that accurately describe the structure and thermodynamic pressure of heptane and toluene at a range of different resolutions, we investigate the impact of bottom-up coarse-graining upon thermodynamic properties. In particular, we demonstrate that U{sub V} accounts for the reduced cohesion in the CG models. Finally, we observe that bottom-up coarse-graining introduces subtle correlations between the resolution, the cohesive energy density, and the “simplicity” of the model.
Hughes, Steven J.; Xi, Liqiang; Raja, Siva; Gooding, William; Cole, David J.; Gillanders, William E.; Mikhitarian, Keidi; McCarty, Kenneth; Silver, Susan; Ching, Jesus; McMillan, William; Luketich, James D.; Godfrey, Tony E.
2006-01-01
Objective: To develop a fully automated, rapid, molecular-based assay that accurately and objectively evaluates sentinel lymph nodes (SLN) from breast cancer patients. Summary Background Data: Intraoperative analysis for the presence of metastatic cancer in SLNs from breast cancer patients lacks sensitivity. Even with immunohistochemical staining (IHC) and time-consuming review, alarming discordance in the interpretation of SLN has been observed. Methods: A total of 43 potential markers were evaluated for the ability to accurately characterize lymph node specimens from breast cancer patients as compared with complete histologic analysis including IHC. Selected markers then underwent external validation on 90 independent SLN specimens using rapid, multiplex quantitative reverse transcription-polymerase chain reaction (QRT-PCR) assays. Finally, 18 SLNs were analyzed using a completely automated RNA isolation, reverse transcription, and quantitative PCR instrument (GeneXpert). Results: Following analysis of potential markers, promising markers were evaluated to establish relative level of expression cutoff values that maximized classification accuracy. A validation set of 90 SLNs from breast cancer patients was prospectively characterized using 4 markers individually or in combinations, and the results compared with histologic analysis. A 2-marker assay was found to be 97.8% accurate (94% sensitive, 100% specific) compared with histologic analysis. The fully automated GeneXpert instrument produced comparable and reproducible results in less than 35 minutes. Conclusions: A rapid, fully automated QRT-PCR assay definitively characterizes breast cancer SLN with accuracy equal to conventional pathology. This approach is superior to intraoperative SLN analysis and can provide standardized, objective results to assist in pathologic diagnosis. PMID:16495705
Accurate path integral molecular dynamics simulation of ab-initio water at near-zero added cost
NASA Astrophysics Data System (ADS)
Elton, Daniel; Fritz, Michelle; Soler, José; Fernandez-Serra, Marivi
It is now established that nuclear quantum motion plays an important role in determining water's structure and dynamics. These effects are important to consider when evaluating DFT functionals and attempting to develop better ones for water. The standard way of treating nuclear quantum effects, path integral molecular dynamics (PIMD), multiplies the number of energy/force calculations by the number of beads, which is typically 32. Here we introduce a method whereby PIMD can be incorporated into a DFT molecular dynamics simulation at virtually zero cost. The method is based on the cluster (many body) expansion of the energy. We first subtract the DFT monomer energies, using a custom DFT-based monomer potential energy surface. The evolution of the PIMD beads is then performed using only the more-accurate Partridge-Schwenke monomer energy surface. The DFT calculations are done using the centroid positions. Various bead thermostats can be employed to speed up the sampling of the quantum ensemble. The method bears some resemblance to multiple timestep algorithms and other schemes used to speed up PIMD with classical force fields. We show that our method correctly captures some of key effects of nuclear quantum motion on both the structure and dynamics of water. We acknowledge support from DOE Award No. DE-FG02-09ER16052 (D.E.) and DOE Early Career Award No. DE-SC0003871 (M.V.F.S.).
Filizola, Marta
2009-01-01
For years conventional drug design at G-protein coupled receptors (GPCRs) has mainly focused on the inhibition of a single receptor at a usually well-defined ligand-binding site. The recent discovery of more and more physiologically relevant GPCR dimers/oligomers suggests that selectively targeting these complexes or designing small molecules that inhibit receptor-receptor interactions might provide new opportunities for novel drug discovery. To uncover the fundamental mechanisms and dynamics governing GPCR dimerization/oligomerization, it is crucial to understand the dynamic process of receptor-receptor association, and to identify regions that are suitable for selective drug binding. This minireview highlights current progress in the development of increasingly accurate dynamic molecular models of GPCR oligomers based on structural, biochemical, and biophysical information that has recently appeared in the literature. In view of this new information, there has never been a more exciting time for computational research into GPCRs than at present. Information-driven modern molecular models of GPCR complexes are expected to efficiently guide the rational design of GPCR oligomer-specific drugs, possibly allowing researchers to reach for the high-hanging fruits in GPCR drug discovery, i.e. more potent and selective drugs for efficient therapeutic interventions. PMID:19465029
Molecular dynamics simulation of dextran extension by constant force in single molecule AFM.
Neelov, Igor M; Adolf, David B; McLeish, Tom C B; Paci, Emanuele
2006-11-15
The extension of 1-6 polysaccharides has been studied in a series of recent single molecule AFM experiments. For dextran, a key finding was the existence of a plateau in the force-extension curve at forces between 700 and 1000 pN. We studied the extension of the dextran 10-mer under constant force using atomistic simulation with various force fields. All the force fields reproduce the experimental plateau on the force-extension curve. With AMBER94 and AMBER-GLYCAM04 force fields the plateau can be explained by a transition of the glucopyranose rings in the dextran monomers from the chair ((4)C(1)) to the inverted chair ((1)C(4)) conformation while other processes occur at smaller (rotation around C5-C6 bond) or higher (chairs to boat transitions) forces. The CHARMM force field provides a different picture which associates the occurrence of the plateau to chair-boat transitions of the glucopyranose rings. PMID:16950842
NASA Astrophysics Data System (ADS)
Yu, Bingwu; van Ingen, Hugo; Freedberg, Darón I.
2013-03-01
Strong 1H-1H coupling can significantly reduce the accuracy of 1JCH measured from frequency differences in coupled HSQC spectra. Although accurate 1JCH values can be extracted from spectral simulation, it would be more convenient if the same accurate 1JCH values can be obtained experimentally. Furthermore, simulations reach their limit for residual dipolar coupling (RDC) measurement, as many significant, but immeasurable RDCs are introduced into the spin system when a molecule is weakly aligned, thus it is impossible to have a model spin system that truly represents the real spin system. Here we report a new J modulated method, constant-time INEPT CT-HSQC (CTi-CT-HSQC), to accurately measure one-bond scalar coupling constant and RDCs without strong coupling interference. In this method, changing the spacing between the two 180° pulses during a constant time INEPT period selectively modulates heteronuclear coupling in quantitative J fashion. Since the INEPT delays for measuring one-bond carbon-proton spectra are short compared to 3JHH, evolution due to (strong) 1H-1H coupling is marginal. The resulting curve shape is practically independent of 1H-1H coupling and only correlated to the heteronuclear coupling evolution. Consequently, an accurate 1JCH can be measured even in the presence of strong coupling. We tested this method on N-acetyl-glucosamine and mannose whose apparent isotropic 1JCH values are significantly affected by strong coupling with other methods. Agreement to within 0.5 Hz or better is found between 1JCH measured by this method and previously published simulation data. We further examined the strong coupling effects on RDC measurements and observed an error up to 100% for one bond RDCs using coupled HSQC in carbohydrates. We demonstrate that RDCs can be obtained with higher accuracy by CTi-CT-HSQC, which compensates the limitation of simulation method.
SPARC (SPARC Performs Automated Reasoning in Chemistry) chemical reactivity models were extended to calculate hydrolysis rate constants for carboxylic acid ester and phosphate ester compounds in aqueous non- aqueous and systems strictly from molecular structure. The energy diffe...
Dunning, T.H. , Jr.; Peterson, K.A.
1998-03-01
The convergence of Mo/ller{endash}Plesset perturbation expansions (MP2{endash}MP4/MP5) for the spectroscopic constants of a selected set of diatomic molecules (BH, CH, HF, N{sub 2}, CO, and F{sub 2}) has been investigated. It was found that the second-order perturbation contributions to the spectroscopic constants are strongly dependent on basis set, more so for HF and CO than for BH. The MP5 contributions for HF were essentially zero for the cc-pVDZ basis set, but increased significantly with basis set illustrating the difficulty of using small basis sets as benchmarks for correlated calculations. The convergence behavior of the {ital exact} Mo/ller{endash}Plesset perturbation expansions were investigated using estimates of the {ital complete basis set limits} obtained using large correlation consistent basis sets. For BH and CH, the perturbation expansions of the spectroscopic constants converge monotonically toward the experimental values, while for HF, N{sub 2}, CO, and F{sub 2}, the expansions oscillate about the experimental values. The perturbation expansions are, in general, only slowly converging and, for HF, N{sub 2}, CO, and F{sub 2}, appear to be far from convergence at MP4. In fact, for HF, N{sub 2}, and CO, the errors in the calculated spectroscopic constants for the MP4 method are {ital larger} than those for the MP2 method (the only exception is D{sub e}). The current study, combined with other recent studies, raises serious doubts about the use of Mo/ller{endash}Plesset perturbation theory to describe electron correlation effects in atomic and molecular calculations. {copyright} {ital 1998 American Institute of Physics.}
Rate Constant Change of Photo Reaction of Bacteriorhodopsin Observed in Trimeric Molecular System.
Tsujiuchi, Yutaka; Masumoto, Hiroshi; Goto, Takashi
2016-04-01
To elucidate the time evolution of photo reaction of bacteriorhodopsin in glycerol mixed purple membrane at around 196 K under irradiation by red light, a kinetic model was constructed. The change of absorption with irradiation at times of 560 nm and 412 nm was analyzed for the purpose of determining reaction rates of photo reaction of bacteriorhodopsin and its product M intermediate. In this study it is shown that reaction rates of conversion from bacteriorhodopsin to the M intermediate can be explained by a set of linear differential equations. This model analysis concludes that bacteriorhodopsin in which constitutes a trimer unit with other two bacteriorhodopsin molecules changes into M intermediates in the 1.73 of reaction rate, in the initial step, and according to the number of M intermediate in a trimer unit, from three to one, the reaction rate of bacteriorhodopsin into M intermediates smaller as 1.73, 0.80, 0.19 which caused by influence of inter-molecular interaction between bacteriorhodopsin. PMID:27451646
NASA Technical Reports Server (NTRS)
Lee, Timothy J.; Dateo, Christopher E.
2005-01-01
The singles and doubles coupled-cluster method that includes a perturbational estimate of connected triple excitations, denoted CCSD(T), has been used, in conjunction with approximate integral techniques, to compute highly accurate rovibrational spectroscopic constants of cyclopropenylidene, C3H2. The approximate integral technique was proposed in 1994 by Rendell and Lee in order to avoid disk storage and input/output bottlenecks, and today it will also significantly aid in the development of algorithms for distributed memory, massively parallel computer architectures. It is shown in this study that use of approximate integrals does not impact the accuracy of CCSD(T) calculations. In addition, the most accurate spectroscopic data yet for C3H2 is presented based on a CCSD(T)/cc-pVQZ quartic force field that is modified to include the effects of core-valence electron correlation. Cyclopropenylidene is of great astronomical and astrobiological interest because it is the smallest aromatic ringed compound to be positively identified in the interstellar medium, and is thus involved in the prebiotic processing of carbon and hydrogen. The singles and doubles coupled-cluster method that includes a perturbational estimate of
Ovchinnikov, Victor; Nam, Kwangho; Karplus, Martin
2016-08-25
A method is developed to obtain simultaneously free energy profiles and diffusion constants from restrained molecular simulations in diffusive systems. The method is based on low-order expansions of the free energy and diffusivity as functions of the reaction coordinate. These expansions lead to simple analytical relationships between simulation statistics and model parameters. The method is tested on 1D and 2D model systems; its accuracy is found to be comparable to or better than that of the existing alternatives, which are briefly discussed. An important aspect of the method is that the free energy is constructed by integrating its derivatives, which can be computed without need for overlapping sampling windows. The implementation of the method in any molecular simulation program that supports external umbrella potentials (e.g., CHARMM) requires modification of only a few lines of code. As a demonstration of its applicability to realistic biomolecular systems, the method is applied to model the α-helix ↔ β-sheet transition in a 16-residue peptide in implicit solvent, with the reaction coordinate provided by the string method. Possible modifications of the method are briefly discussed; they include generalization to multidimensional reaction coordinates [in the spirit of the model of Ermak and McCammon (Ermak, D. L.; McCammon, J. A. J. Chem. Phys. 1978, 69, 1352-1360)], a higher-order expansion of the free energy surface, applicability in nonequilibrium systems, and a simple test for Markovianity. In view of the small overhead of the method relative to standard umbrella sampling, we suggest its routine application in the cases where umbrella potential simulations are appropriate. PMID:27135391
Bai, Fang; Liao, Sha; Gu, Junfeng; Jiang, Hualiang; Wang, Xicheng; Li, Honglin
2015-04-27
Metalloproteins, particularly zinc metalloproteins, are promising therapeutic targets, and recent efforts have focused on the identification of potent and selective inhibitors of these proteins. However, the ability of current drug discovery and design technologies, such as molecular docking and molecular dynamics simulations, to probe metal-ligand interactions remains limited because of their complicated coordination geometries and rough treatment in current force fields. Herein we introduce a robust, multiobjective optimization algorithm-driven metalloprotein-specific docking program named MpSDock, which runs on a scheme similar to consensus scoring consisting of a force-field-based scoring function and a knowledge-based scoring function. For this purpose, in this study, an effective knowledge-based zinc metalloprotein-specific scoring function based on the inverse Boltzmann law was designed and optimized using a dynamic sampling and iteration optimization strategy. This optimization strategy can dynamically sample and regenerate decoy poses used in each iteration step of refining the scoring function, thus dramatically improving both the effectiveness of the exploration of the binding conformational space and the sensitivity of the ranking of the native binding poses. To validate the zinc metalloprotein-specific scoring function and its special built-in docking program, denoted MpSDockZn, an extensive comparison was performed against six universal, popular docking programs: Glide XP mode, Glide SP mode, Gold, AutoDock, AutoDock4Zn, and EADock DSS. The zinc metalloprotein-specific knowledge-based scoring function exhibited prominent performance in accurately describing the geometries and interactions of the coordination bonds between the zinc ions and chelating agents of the ligands. In addition, MpSDockZn had a competitive ability to sample and identify native binding poses with a higher success rate than the other six docking programs. PMID:25746437
Watanabe, T; Manz, TA; Sholl, DS
2011-03-24
Molecular simulations have become an important complement to experiments for studying gas adsorption and separation in crystalline nanoporous materials. Conventionally, these simulations use force fields that model adsorbate-pore interactions by assigning point charges to the atoms of the adsorbent. The assignment of framework charges always introduces ambiguity because there are many different choices for defining point charges, even when the true electron density of a material is known. We show how to completely avoid such ambiguity by using the electrostatic potential energy surface (EPES) calculated from plane wave density functional theory (DFT). We illustrate this approach by simulating CO(2) adsorption in four metal-organic frameworks (MOFs): IRMOF-1, ZIE-8, ZIE-90, and Zn(nicotinate)(2). The resulting CO(2) adsorption isotherms are insensitive to the exchange-correlation functional used in the DFT calculation of the EPES but are sensitive to changes in the crystal structure and lattice parameters. Isotherms computed from the DFT EPES are compared to those computed from several point charge models. This comparison makes possible, for the first time, an unbiased assessment of the accuracy of these point charge models for describing adsorption in MOFs. We find an unusually high Henry's constant (109 mmol/g.bar) and intermediate isosteric heat of adsorption (34.9 kJ/mol) for Zn(nicotinate)(2), which makes it a potentially attractive mateiial for CO(2) adsorption applications.
NASA Astrophysics Data System (ADS)
Sangiovanni, D. G.; Hellman, O.; Alling, B.; Abrikosov, I. A.
2016-03-01
We revisit the color-diffusion algorithm [Aeberhard et al., Phys. Rev. Lett. 108, 095901 (2012), 10.1103/PhysRevLett.108.095901] in non equilibrium ab initio molecular dynamics (NE-AIMD) and propose a simple efficient approach for the estimation of monovacancy jump rates in crystalline solids at temperatures well below melting. Color-diffusion applied to monovacancy migration entails that one lattice atom (colored atom) is accelerated toward the neighboring defect site by an external constant force F. Considering bcc molybdenum between 1000 and 2800 K as a model system, NE-AIMD results show that the colored-atom jump rate kNE increases exponentially with the force intensity F , up to F values far beyond the linear-fitting regime employed previously. Using a simple model, we derive an analytical expression which reproduces the observed kNE(F ) dependence on F . Equilibrium rates extrapolated by NE-AIMD results are in excellent agreement with those of unconstrained dynamics. The gain in computational efficiency achieved with our approach increases rapidly with decreasing temperatures and reaches a factor of 4 orders of magnitude at the lowest temperature considered in the present study.
Barone, Vincenzo; Biczysko, Malgorzata Bloino, Julien; Puzzarini, Cristina
2014-07-21
Oxirane derivatives are the most used benchmarks for chiroptical spectroscopies in view of their small size and relative rigidity. The molecular structure, vibrational harmonic and anharmonic frequencies, and infrared intensities of the ground electronic states are analyzed in this paper. Equilibrium structure and harmonic force fields have been evaluated by means of high-level quantum-chemical calculations at the coupled-cluster level including single and double excitations together with a perturbative treatment of triples (CCSD(T)). Extrapolation to the complete basis-set limit as well as core-correlation effects have also been taken into account. Anharmonic contributions have been computed at the CCSD(T)/cc-pVTZ level for trans-2,3-dideuterooxirane. These data can serve as references to evaluate the accuracy of less expensive computational approaches rooted in the density functional theory (DFT). The latter have been used within hybrid CC/DFT approaches, which have been applied to simulate fully anharmonic infrared (IR) spectra. Finally, the best theoretical estimates of the equilibrium structures and vibrational wavenumbers are compared to the most accurate experimental data and show in all cases very good agreement, i.e., within 0.001 Å, 0.1 deg, 10 cm{sup −1}, and 0.5 km mol{sup −1}, for bond lengths, angles, wavenumbers, and IR intensities, respectively.
Flynn, Jullien M; Brown, Emily A; Chain, Frédéric J J; MacIsaac, Hugh J; Cristescu, Melania E
2015-01-01
Metabarcoding has the potential to become a rapid, sensitive, and effective approach for identifying species in complex environmental samples. Accurate molecular identification of species depends on the ability to generate operational taxonomic units (OTUs) that correspond to biological species. Due to the sometimes enormous estimates of biodiversity using this method, there is a great need to test the efficacy of data analysis methods used to derive OTUs. Here, we evaluate the performance of various methods for clustering length variable 18S amplicons from complex samples into OTUs using a mock community and a natural community of zooplankton species. We compare analytic procedures consisting of a combination of (1) stringent and relaxed data filtering, (2) singleton sequences included and removed, (3) three commonly used clustering algorithms (mothur, UCLUST, and UPARSE), and (4) three methods of treating alignment gaps when calculating sequence divergence. Depending on the combination of methods used, the number of OTUs varied by nearly two orders of magnitude for the mock community (60–5068 OTUs) and three orders of magnitude for the natural community (22–22191 OTUs). The use of relaxed filtering and the inclusion of singletons greatly inflated OTU numbers without increasing the ability to recover species. Our results also suggest that the method used to treat gaps when calculating sequence divergence can have a great impact on the number of OTUs. Our findings are particularly relevant to studies that cover taxonomically diverse species and employ markers such as rRNA genes in which length variation is extensive. PMID:26078860
Timr, Štěpán; Brabec, Jiří; Bondar, Alexey; Ryba, Tomáš; Železný, Miloš; Lazar, Josef; Jungwirth, Pavel
2015-07-30
Several methods based on single- and two-photon fluorescence detected linear dichroism have recently been used to determine the orientational distributions of fluorescent dyes in lipid membranes. However, these determinations relied on simplified descriptions of nonlinear anisotropic properties of the dye molecules, using a transition dipole-moment-like vector instead of an absorptivity tensor. To investigate the validity of the vector approximation, we have now carried out a combination of computer simulations and polarization microscopy experiments on two representative fluorescent dyes (DiI and F2N12S) embedded in aqueous phosphatidylcholine bilayers. Our results indicate that a simplified vector-like treatment of the two-photon transition tensor is applicable for molecular geometries sampled in the membrane at ambient conditions. Furthermore, our results allow evaluation of several distinct polarization microscopy techniques. In combination, our results point to a robust and accurate experimental and computational treatment of orientational distributions of DiI, F2N12S, and related dyes (including Cy3, Cy5, and others), with implications to monitoring physiologically relevant processes in cellular membranes in a novel way. PMID:26146848
Colmenares, Pedro J; López, Floralba; Olivares-Rivas, Wilmer
2009-12-01
We carried out a molecular-dynamics (MD) study of the self-diffusion tensor of a Lennard-Jones-type fluid, confined in a slit pore with attractive walls. We developed Bayesian equations, which modify the virtual layer sampling method proposed by Liu, Harder, and Berne (LHB) [P. Liu, E. Harder, and B. J. Berne, J. Phys. Chem. B 108, 6595 (2004)]. Additionally, we obtained an analytical solution for the corresponding nonhomogeneous Langevin equation. The expressions found for the mean-squared displacement in the layers contain naturally a modification due to the mean force in the transverse component in terms of the anisotropic diffusion constants and mean exit time. Instead of running a time consuming dual MD-Langevin simulation dynamics, as proposed by LHB, our expression was used to fit the MD data in the entire survival time interval not only for the parallel but also for the perpendicular direction. The only fitting parameter was the diffusion constant in each layer. PMID:20365134
NASA Astrophysics Data System (ADS)
Colmenares, Pedro J.; López, Floralba; Olivares-Rivas, Wilmer
2009-12-01
We carried out a molecular-dynamics (MD) study of the self-diffusion tensor of a Lennard-Jones-type fluid, confined in a slit pore with attractive walls. We developed Bayesian equations, which modify the virtual layer sampling method proposed by Liu, Harder, and Berne (LHB) [P. Liu, E. Harder, and B. J. Berne, J. Phys. Chem. B 108, 6595 (2004)]. Additionally, we obtained an analytical solution for the corresponding nonhomogeneous Langevin equation. The expressions found for the mean-squared displacement in the layers contain naturally a modification due to the mean force in the transverse component in terms of the anisotropic diffusion constants and mean exit time. Instead of running a time consuming dual MD-Langevin simulation dynamics, as proposed by LHB, our expression was used to fit the MD data in the entire survival time interval not only for the parallel but also for the perpendicular direction. The only fitting parameter was the diffusion constant in each layer.
NASA Astrophysics Data System (ADS)
Oba, Yuki; Kawatsu, Tsutomu; Tachikawa, Masanori
2016-08-01
The on-the-fly ab initio density functional path integral molecular dynamics (PIMD) simulations, which can account for both the nuclear quantum effect and thermal effect, were carried out to evaluate the structures and "reduced" isotropic hyperfine coupling constants (HFCCs) for muoniated and hydrogenated acetone radicals (2-muoxy-2-propyl and 2-hydoxy-2-propyl) in vacuo. The reduced HFCC value from a simple geometry optimization calculation without both the nuclear quantum effect and thermal effect is -8.18 MHz, and that by standard ab initio molecular dynamics simulation with only the thermal effect and without the nuclear quantum effect is 0.33 MHz at 300 K, where these two methods cannot distinguish the difference between muoniated and hydrogenated acetone radicals. In contrast, the reduced HFCC value of the muoniated acetone radical by our PIMD simulation is 32.1 MHz, which is about 8 times larger than that for the hydrogenated radical of 3.97 MHz with the same level of calculation. We have found that the HFCC values are highly correlated with the local molecular structures; especially, the Mu—O bond length in the muoniated acetone radical is elongated due to the large nuclear quantum effect of the muon, which makes the expectation value of the HFCC larger. Although our PIMD result calculated in vacuo is about 4 times larger than the measured experimental value in aqueous solvent, the ratio of these HFCC values between muoniated and hydrogenated acetone radicals in vacuo is in reasonable agreement with the ratio of the experimental values in aqueous solvent (8.56 MHz and 0.9 MHz); the explicit presence of solvent molecules has a major effect on decreasing the reduced muon HFCC of in vacuo calculations for the quantitative reproduction.
NASA Astrophysics Data System (ADS)
Fortenberry, Ryan C.; Lee, Timothy J.; Müller, Holger S. P.
2015-11-01
Silacyclopropynylidene, SiC2, is a known and highly abundant circumstellar molecule. Its spectrum has been established as a major component of lines observed toward the carbon-rich star IRC +10216 (CW Leonis). It has been detected in its low-lying v3 = 1 and 2 vibrational states as well as in various isotopic compositions. Increasing sensitivity and spatial resolution will enable many more emission or absorption lines to be detected. In order to detect new molecular species, unassigned lines of known species must be identified. This work uses established ab initio quartic force fields to produce data necessary for this classification of lines related to SiC2. Agreement between the theoretical vibrational frequencies and known rotational and spectroscopic constants is quite good, as good as 5 cm-1 and 3 MHz, respectively in some cases. In addition, experimentally unknown vibrational frequencies and rotational constants are provided for the first overtones and combination bands in addition to 3ν3, the second overtone of the low-lying antisymmetric stretch/carbide rotation mode. Frequencies of v3 = 3 low-J rotational transitions of the main isotopic species are also estimated from published data for v3 ≤ 2. Further, we determine rotational and centrifugal distortion parameters for which in most cases vibrational effects due to the ν3 mode were reduced to first, and in several cases also to second order. These values may approximate equilibrium values better than the ground state values. The data produced herein will aid in the experimental and observational characterization of this known astromolecule in order to identify some of the unassigned lines for a known entity.
Hayes, Malcolm; Peckova, Kvetoslava; Martinek, Petr; Hora, Milan; Kalusova, Kristyna; Straka, Lubomir; Daum, Ondrej; Kokoskova, Bohuslava; Rotterova, Pavla; Pivovarčikova, Kristyna; Branzovsky, Jindrich; Dubova, Magdalena; Vesela, Pavla; Michal, Michal; Hes, Ondrej
2015-03-01
tumours can only be sub-classified accurately by multi-parameter molecular-genetic analysis. PMID:25544614
Constant pH Molecular Dynamics Reveals pH-Modulated Binding of Two Small-Molecule BACE1 Inhibitors.
Ellis, Christopher R; Tsai, Cheng-Chieh; Hou, Xinjun; Shen, Jana
2016-03-17
Targeting β-secretase (BACE1) with small-molecule inhibitors offers a promising route for treatment of Alzheimer's disease. However, the intricate pH dependence of BACE1 function and inhibitor efficacy has posed major challenges for structure-based drug design. Here we investigate two structurally similar BACE1 inhibitors that have dramatically different inhibitory activity using continuous constant pH molecular dynamics (CpHMD). At high pH, both inhibitors are stably bound to BACE1; however, within the enzyme active pH range, only the iminopyrimidinone-based inhibitor remains bound, while the aminothiazine-based inhibitor becomes partially dissociated following the loss of hydrogen bonding with the active site and change of the 10s loop conformation. The drastically lower activity of the second inhibitor is due to the protonation of a catalytic aspartate and the lack of a propyne tail. This work demonstrates that CpHMD can be used for screening pH-dependent binding profiles of small-molecule inhibitors, providing a new tool for structure-based drug design and optimization. PMID:26905811
NASA Astrophysics Data System (ADS)
Ma, Zhonghua; Zhang, Yanli; Tuckerman, Mark E.
2012-07-01
It is generally believed that studies of liquid water using the generalized gradient approximation to density functional theory require dispersion corrections in order to obtain reasonably accurate structural and dynamical properties. Here, we report on an ab initio molecular dynamics study of water in the isothermal-isobaric ensemble using a converged discrete variable representation basis set and an empirical dispersion correction due to Grimme [J. Comp. Chem. 27, 1787 (2006)], 10.1002/jcc.20495. At 300 K and an applied pressure of 1 bar, the density obtained without dispersion corrections is approximately 0.92 g/cm3 while that obtained with dispersion corrections is 1.07 g/cm3, indicating that the empirical dispersion correction overestimates the density by almost as much as it is underestimated without the correction for this converged basis. Radial distribution functions exhibit a loss of structure in the second solvation shell. Comparison of our results with other studies using the same empirical correction suggests the cause of the discrepancy: the Grimme dispersion correction is parameterized for use with a particular basis set; this parameterization is sensitive to this choice and, therefore, is not transferable to other basis sets.
Kim, Yong-Hyun; Kim, Ki-Hyun
2014-05-16
Accurate values for the Henry's law constants are essential to describe the environmental dynamics of a solute, but substantial errors are recognized in many reported data due to practical difficulties in measuring solubility and/or vapor pressure. Despite such awareness, validation of experimental approaches has scarcely been made. An experimental approach based on thermal desorption-gas chromatography-mass spectrometery (TD-GC-MS) method was developed to concurrently allow the accurate determination of target compounds from the headspace and aqueous samples in closed equilibrated system. The analysis of six aromatics and eight non-aromatic oxygenates was then carried out in a static headspace mode. An estimation of the potential bias and mass balance (i.e., sum of mass measured individually from gas and liquid phases vs. the mass initially added to the system) demonstrates compound-specific phase dependency so that the best results are obtained by aqueous (less soluble aromatics) and headspace analysis (more soluble non-aromatics). Accordingly, we were able to point to the possible sources of biases in previous studies and provide the best estimates for the Henry's constants (Matm(-1)): benzene (0.17), toluene (0.15), p-xylene (0.13), m-xylene (0.13), o-xylene (0.19), styrene (0.27); propionaldehyde (9.26), butyraldehyde (6.19), isovaleraldehyde (2.14), n-valeraldehyde (3.98), methyl ethyl ketone (10.5), methyl isobutyl ketone (3.93), n-butyl acetate (2.41), and isobutyl alcohol (22.2). PMID:24704185
2015-01-01
The structural similarity between the primary molecules of voltage-gated Na and K channels (alpha subunits) and activation gating in the Hodgkin-Huxley model is brought into full agreement by increasing the model's sodium kinetics to fourth order (m3 → m4). Both structures then virtually imply activation gating by four independent subprocesses acting in parallel. The kinetics coalesce in four-dimensional (4D) cubic diagrams (16 states, 32 reversible transitions) that show the structure to be highly failure resistant against significant partial loss of gating function. Rate constants, as fitted in phase plot data of retinal ganglion cell excitation, reflect the molecular nature of the gating transitions. Additional dimensions (6D cubic diagrams) accommodate kinetically coupled sodium inactivation and gating processes associated with beta subunits. The gating transitions of coupled sodium inactivation appear to be thermodynamically irreversible; response to dielectric surface charges (capacitive displacement) provides a potential energy source for those transitions and yields highly energy-efficient excitation. A comparison of temperature responses of the squid giant axon (apparently Arrhenius) and mammalian channel gating yields kinetic Q10 = 2.2 for alpha unit gating, whose transitions are rate-limiting at mammalian temperatures; beta unit kinetic Q10 = 14 reproduces the observed non-Arrhenius deviation of mammalian gating at low temperatures; the Q10 of sodium inactivation gating matches the rate-limiting component of activation gating at all temperatures. The model kinetics reproduce the physiologically large frequency range for repetitive firing in ganglion cells and the physiologically observed strong temperature dependence of recovery from inactivation. PMID:25867741
Fohlmeister, Jürgen F
2015-06-01
The structural similarity between the primary molecules of voltage-gated Na and K channels (alpha subunits) and activation gating in the Hodgkin-Huxley model is brought into full agreement by increasing the model's sodium kinetics to fourth order (m(3) → m(4)). Both structures then virtually imply activation gating by four independent subprocesses acting in parallel. The kinetics coalesce in four-dimensional (4D) cubic diagrams (16 states, 32 reversible transitions) that show the structure to be highly failure resistant against significant partial loss of gating function. Rate constants, as fitted in phase plot data of retinal ganglion cell excitation, reflect the molecular nature of the gating transitions. Additional dimensions (6D cubic diagrams) accommodate kinetically coupled sodium inactivation and gating processes associated with beta subunits. The gating transitions of coupled sodium inactivation appear to be thermodynamically irreversible; response to dielectric surface charges (capacitive displacement) provides a potential energy source for those transitions and yields highly energy-efficient excitation. A comparison of temperature responses of the squid giant axon (apparently Arrhenius) and mammalian channel gating yields kinetic Q10 = 2.2 for alpha unit gating, whose transitions are rate-limiting at mammalian temperatures; beta unit kinetic Q10 = 14 reproduces the observed non-Arrhenius deviation of mammalian gating at low temperatures; the Q10 of sodium inactivation gating matches the rate-limiting component of activation gating at all temperatures. The model kinetics reproduce the physiologically large frequency range for repetitive firing in ganglion cells and the physiologically observed strong temperature dependence of recovery from inactivation. PMID:25867741
NASA Astrophysics Data System (ADS)
Velazquez, Hector A.; Hamelberg, Donald
2015-02-01
Cis-trans isomerization of peptidyl-prolyl bonds of the protein backbone plays an important role in numerous biological processes. Cis-trans isomerization can be the rate-limiting step due its extremely slow dynamics, compared to the millisecond time scale of many processes, and is catalyzed by a widely studied family of peptidyl-prolyl cis-trans isomerase enzymes. Also, mechanical forces along the peptide chain can speed up the rate of isomerization, resulting in "mechanical catalysis," and have been used to study peptidyl-prolyl cis-trans isomerization and other mechanical properties of proteins. Here, we use constant force molecular dynamics simulations to study the dynamical effects of phosphorylation on serine/threonine-proline protein motifs that are involved in the function of many proteins and have been implicated in many aberrant biological processes. We show that the rate of cis-trans isomerization is slowed down by phosphorylation, in excellent agreement with experiments. We use a well-grounded theory to describe the force dependent rate of isomerization. The calculated rates at zero force are also in excellent agreement with experimentally measured rates, providing additional validation of the models and force field parameters. Our results suggest that the slowdown in the rate upon phosphorylation is mainly due to an increase in the friction along the peptidyl-prolyl bond angle during isomerization. Our results provide a microscopic description of the dynamical effects of post-translational phosphorylation on cis-trans isomerization and insights into the properties of proteins under tension.
Technology Transfer Automated Retrieval System (TEKTRAN)
The disaccharide, alpha/beta-maltose, has been studied using constant energy ab initio molecular dynamics at the B3LYP/6-31+G* COSMO (solvent) level of theory. Maltose is of particular interest as the variation in glycosidic dihedral angles is dependent upon the starting hydroxyl conformation. Tha...
Meng, Qingyong Chen, Jun Zhang, Dong H.
2015-09-14
The ring polymer molecular dynamics (RPMD) calculations are performed to calculate rate constants for the title reaction on the recently constructed potential energy surface based on permutation invariant polynomial (PIP) neural-network (NN) fitting [J. Li et al., J. Chem. Phys. 142, 204302 (2015)]. By inspecting convergence, 16 beads are used in computing free-energy barriers at 300 K ≤ T ≤ 1000 K, while different numbers of beads are used for transmission coefficients. The present RPMD rates are in excellent agreement with quantum rates computed on the same potential energy surface, as well as with the experimental measurements, demonstrating further that the RPMD is capable of producing accurate rates for polyatomic chemical reactions even at rather low temperatures.
The cosmological constant problem
Dolgov, A.D.
1989-05-01
A review of the cosmological term problem is presented. Baby universe model and the compensating field model are discussed. The importance of more accurate data on the Hubble constant and the Universe age is stressed. 18 refs.
Kanai, Y; Takeuchi, N
2009-10-14
We revisit the molecular line growth mechanism of styrene on the hydrogenated Si(001) 2x1 surface. In particular, we investigate the energetics of the radical chain reaction mechanism by means of diffusion quantum Monte Carlo (QMC) and density functional theory (DFT) calculations. For the exchange correlation (XC) functional we use the non-empirical generalized-gradient approximation (GGA) and meta-GGA. We find that the QMC result also predicts the intra dimer-row growth of the molecular line over the inter dimer-row growth, supporting the conclusion based on DFT results. However, the absolute magnitudes of the adsorption and reaction energies, and the heights of the energy barriers differ considerably between the QMC and DFT with the GGA/meta-GGA XC functionals.
NASA Astrophysics Data System (ADS)
Osei-Kuffuor, Daniel; Fattebert, Jean-Luc
2014-01-01
We present the first truly scalable first-principles molecular dynamics algorithm with O(N) complexity and controllable accuracy, capable of simulating systems with finite band gaps of sizes that were previously impossible with this degree of accuracy. By avoiding global communications, we provide a practical computational scheme capable of extreme scalability. Accuracy is controlled by the mesh spacing of the finite difference discretization, the size of the localization regions in which the electronic wave functions are confined, and a cutoff beyond which the components of the overlap matrix can be omitted when computing selected elements of its inverse. We demonstrate the algorithm's excellent parallel scaling for up to 101 952 atoms on 23 328 processors, with a wall-clock time of the order of 1 min per molecular dynamics time step and numerical error on the forces of less than 7×10-4 Ha/Bohr.
Osei-Kuffuor, Daniel; Fattebert, Jean-Luc
2014-01-01
We present the first truly scalable first-principles molecular dynamics algorithm with O(N) complexity and controllable accuracy, capable of simulating systems with finite band gaps of sizes that were previously impossible with this degree of accuracy. By avoiding global communications, we provide a practical computational scheme capable of extreme scalability. Accuracy is controlled by the mesh spacing of the finite difference discretization, the size of the localization regions in which the electronic wave functions are confined, and a cutoff beyond which the components of the overlap matrix can be omitted when computing selected elements of its inverse. We demonstrate the algorithm's excellent parallel scaling for up to 101 952 atoms on 23 328 processors, with a wall-clock time of the order of 1 min per molecular dynamics time step and numerical error on the forces of less than 7x10^{-4} Ha/Bohr.
O'Brien, Leah C.; Cao, Hong; O'Brien, James J.
2001-05-01
High-resolution intracavity laser spectroscopy (ILS) absorption measurements have been made on the b-X oxygen electronic transition (the A-band) which has bandheads occurring in the region of 13 165 cm(-1). The positions of the lines were determined to an accuracy that is based on calibration with I(2) absorption lines using the Laboratoire Aimé Cotton (Orsay) Atlas as reference. Based on the ILS measurements and the more accurately determined positions given by L. R. Brown and C. Plymate (J. Mol. Spectrosc. 199, 166-179 (2000)) and with the (3)Sigma(g)(-) ground state molecular constants fixed at the values determined by G. Rouillé et al. (J. Mol. Spectrosc. 154, 372-382 (1992)), the following values (in cm(-1)) were found for the molecular constants: T(0)=13122.2524(1); B(0)=1.391244(2); D(0)=5.352(4)x10(-6); and H(0)=-1.2(2)x10(-11). These results are compared with values derived from fits of the line positions listed in several other studies of this transition. Copyright 2001 Academic Press. PMID:11336527
NASA Astrophysics Data System (ADS)
Wang, Jie-Min; Feng, Heng-Qiang; Sun, Jin-Feng; Shi, De-Heng
2012-02-01
The potential energy curves (PECs) of three low-lying electronic states (X1Σg+, w3Δu, and W1Δu) of P2 molecule are investigated using the full valence complete active space self-consistent field (CASSCF) method followed by the highly accurate valence internally contracted multireference configuration interaction (MRCI) approach in conjunction with the correlation-consistent basis set in the valence range. The PECs of the electronic states involved are modified by the Davidson correction and extrapolated to the complete basis set (CBS) limit. With these PECs, the spectroscopic parameters of the three electronic states are determined and compared in detail with the experimental data. The comparison shows that excellent agreement exists between the present results and the available experimental data. The complete vibrational states are computed for the w3Δu and W1Δu electronic states when the rotational quantum number J equals zero and the vibrational level G(υ), the inertial rotation constant Bυ, and the centrifugal distortion constant Dυ of the first 30 vibrational states are reported, which accord well with the experimental data. The present results show that the two-point extrapolation scheme can obviously improve the quality of spectroscopic parameters and molecular constants.
The route to MBxNyCz molecular wheels: II. Results using accurate functionals and basis sets
NASA Astrophysics Data System (ADS)
Güthler, A.; Mukhopadhyay, S.; Pandey, R.; Boustani, I.
2014-04-01
Applying ab initio quantum chemical methods, molecular wheels composed of metal and light atoms were investigated. High quality basis sets 6-31G*, TZPV, and cc-pVTZ as well as exchange and non-local correlation functionals B3LYP, BP86 and B3P86 were used. The ground-state energy and structures of cyclic planar and pyramidal clusters TiBn (for n = 3-10) were computed. In addition, the relative stability and electronic structures of molecular wheels TiBxNyCz (for x, y, z = 0-10) and MBnC10-n (for n = 2 to 5 and M = Sc to Zn) were determined. This paper sustains a follow-up study to the previous one of Boustani and Pandey [Solid State Sci. 14 (2012) 1591], in which the calculations were carried out at the HF-SCF/STO3G/6-31G level of theory to determine the initial stability and properties. The results show that there is a competition between the 2D planar and the 3D pyramidal TiBn clusters (for n = 3-8). Different isomers of TiB10 clusters were also studied and a structural transition of 3D-isomer into 2D-wheel is presented. Substitution boron in TiB10 by carbon or/and nitrogen atoms enhances the stability and leads toward the most stable wheel TiB3C7. Furthermore, the computations show that Sc, Ti and V at the center of the molecular wheels are energetically favored over other transition metal atoms of the first row.
NASA Astrophysics Data System (ADS)
Osei-Kuffuor, Daniel; Fattebert, Jean-Luc
2014-03-01
We present a truly scalable First-Principles Molecular Dynamics algorithm with O(N) complexity and fully controllable accuracy, capable of simulating systems of sizes that were previously impossible with this degree of accuracy. By avoiding global communication, we have extended W. Kohn's condensed matter ``nearsightedness'' principle to a practical computational scheme capable of extreme scalability. Accuracy is controlled by the mesh spacing of the finite difference discretization, the size of the localization regions in which the electronic wavefunctions are confined, and a cutoff beyond which the components of the overlap matrix can be omitted when computing selected elements of its inverse. We demonstrate the algorithm's excellent parallel scaling for up to 100,000 atoms on 100,000 processors, with a wall-clock time of the order of one minute per molecular dynamics time step. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.
NASA Astrophysics Data System (ADS)
Rustad, James R.; Felmy, Andrew R.; Hay, Benjamin P.
1996-05-01
A new approach to estimating stability constants for proton binding in multisite surface complexation models is presented. The method is based on molecular statics computation of energies for the formation of proton vacancies and interstitials in ideal periodic slabs representing the (100), (110), (010), (001), and (021) surfaces of goethite. Gas-phase energies of clusters representing the hydrolysis products of ferric iron are calculated using the same potential energy functions used for the surface. These energies are linearly related to the hydrolysis constants for ferric iron in aqueous solution. Stability constants for proton binding at goethite surfaces are estimated by assuming the same log K- Δ E relationship for goethite surface protonation reactions. These stability constants predict a pH of zero charge of 8.9, in adequate agreement with measurements on CO 2-free goethite. The estimated stability constants differ significantly from previous estimations based on Pauling bond strength. We find that nearly all the surface oxide ions are reactive; nineteen of the twenty-six surface sites investigated have log Kint between 7.7 and 9.4. This implies a site density between fifteen and sixteen reactive sites/nm for crystals dominated by (110) and (021) crystal faces.
Rustad, J.R.; Felmy, A.R.; Hay, B.P.
1996-05-01
A new approach to estimating stability constants for proton binding in multisite surface complexation models is presented. The method is based on molecular statics computation of energies for the formation of proton vacancies and interstitials in ideal periodic slabs representing the (100), (110), (010), (001), and (021) surfaces of goethite. Gas-phase energies of clusters representing the hydrolysis products of ferric iron are calculated using the same potential energy functions used for the surface. These energies are linearly related to the hydrolysis constants for ferric iron in aqueous solution. Stability constants for proton binding at goethite surfaces are estimated by assuming the same log K-{Delta}E relationship for goethite surface protonation reactions. These stability constants predict a pH of zero charge of 8.9, in adequate agreement with measurements on CO{sub 2}-free goethite. The estimated stability constants differ significantly from previous estimations based on Pauling bond strength. We find that nearly all the surface oxide ions are reactive; nineteen of the twenty-six surface sites investigated have log K{sup int} between 7.7 and 9.4. This implies a site density between fifteen and sixteen reactive sites/nm for crystals dominated by (110) and (021) crystal faces. 39 refs., 8 figs., 4 tabs.
Fang, Wanping; Meinhardt, Lyndel W; Mischke, Sue; Bellato, Cláudia M; Motilal, Lambert; Zhang, Dapeng
2014-01-15
Cacao (Theobroma cacao L.), the source of cocoa, is an economically important tropical crop. One problem with the premium cacao market is contamination with off-types adulterating raw premium material. Accurate determination of the genetic identity of single cacao beans is essential for ensuring cocoa authentication. Using nanofluidic single nucleotide polymorphism (SNP) genotyping with 48 SNP markers, we generated SNP fingerprints for small quantities of DNA extracted from the seed coat of single cacao beans. On the basis of the SNP profiles, we identified an assumed adulterant variety, which was unambiguously distinguished from the authentic beans by multilocus matching. Assignment tests based on both Bayesian clustering analysis and allele frequency clearly separated all 30 authentic samples from the non-authentic samples. Distance-based principle coordinate analysis further supported these results. The nanofluidic SNP protocol, together with forensic statistical tools, is sufficiently robust to establish authentication and to verify gourmet cacao varieties. This method shows significant potential for practical application. PMID:24354624
Just, Pierre-Alexandre; Cazes, Aurélie; Audebourg, Anne; Cessot, Anatole; Pallier, Karine; Danel, Claire; Vacher-Lavenu, Marie-Cécile; Laurent-Puig, Pierre; Terris, Benoît; Blons, Hélène
2012-06-01
EML4-ALK adenocarcinomas constitute a new molecular subgroup of lung tumours that respond very well to crizotinib, an ALK inhibitor. However, the diagnosis of ALK rearrangement in lung cancer is challenging. The aim of this study was to compare the diagnostic accuracy of five different methods in a series of 20 EGFR(wt/wt) lung adenocarcinomas from non- or light- smokers. Multiplex RT-PCR was considered as gold standard and identified four ALK-rearranged tumours among the 20 tested tumours. qRT-PCR got an interpretability rate of 100% and accurately typed all 20 tumours. qRT-PCR from corresponding formalin-fixed paraffin-embedded (FFPE) specimens got an interpretability rate of 65%. Out of the four previously identified ALK-rearranged cases, three were interpretable and two were retrieved using FFPE qRT-PCR. ALK break-apart FISH got an interpretability rate of 60% and accurately typed all of the twelve remaining cases. Anti-ALK immunohistochemistry (IHC) accurately typed all twenty tumours using a cut-off value of strong staining of 100% tumour cells. The 16 non ALK-rearranged tumours got no/light staining in 13 cases, and a moderate staining of 80-100% tumour cells in 3 cases. We then analysed four solid signet-ring lung adenocarcinomas. FFPE qRT-PCR, FISH and immunohistochemistry were concordant in three cases, with positive and negative results in respectively one and two cases. The fourth case, which was positive by FISH and immunohistochemistry but negative by RT-PCR, was shown to have a non-EML4-ALK ALK-rearrangement. As various factors such as RNA quality, fixation quality and type of ALK rearrangement may impede ALK screening, we propose a combined FISH/molecular biology diagnostic algorithm in which anti-ALK immunohistochemistry is used as a pre-screening step. PMID:22153831
Zarycz, M. Natalia C. Provasi, Patricio F.; Sauer, Stephan P. A.
2014-10-21
We discuss the effect of electron correlation on the unexpected differential sensitivity (UDS) in the {sup 1}J(C–H) coupling constant of CH{sub 4} using a decomposition into contributions from localized molecular orbitals and compare with the {sup 1}J(N–H) coupling constant in NH{sub 3}. In particular, we discuss the well known fact that uncorrelated coupled Hartree-Fock (CHF) calculations are not able to reproduce the UDS in methane. For this purpose we have implemented for the first time a localized molecular orbital analysis for the second order polarization propagator approximation with coupled cluster singles and doubles amplitudes—SOPPA(CCSD) in the DALTON program. Comparing the changes in the localized orbital contributions at the correlated SOPPA and SOPPA(CCSD) levels and at the uncorrelated CHF level, we find that the latter overestimates the effect of stretching the bond between the coupled atoms on the contribution to the coupling from the localized bonding orbital between these atoms. This disturbs the subtle balance between the molecular orbital contributions, which lead to the UDS in methane.
Jia, Lijuan; Shen, Zhemin; Su, Pingru
2016-05-01
Fenton oxidation is a promising water treatment method to degrade organic pollutants. In this study, 30 different organic compounds were selected and their reaction rate constants (k) were determined for the Fenton oxidation process. Gaussian09 and Material Studio software sets were used to carry out calculations and obtain values of 10 different molecular descriptors for each studied compound. Ferric-oxyhydroxide coagulation experiments were conducted to determine the coagulation percentage. Based upon the adsorption capacity, all of the investigated organic compounds were divided into two groups (Group A and Group B). The percentage adsorption of organic compounds in Group A was less than 15% (wt./wt.) and that in the Group B was higher than 15% (wt./wt.). For Group A, removal of the compounds by oxidation was the dominant process while for Group B, removal by both oxidation and coagulation (as a synergistic process) took place. Results showed that the relationship between the rate constants (k values) and the molecular descriptors of Group A was more pronounced than for Group B compounds. For the oxidation-dominated process, EHOMO and Fukui indices (f(0)x, f(-)x, f(+)x) were the most significant factors. The influence of bond order was more significant for the synergistic process of oxidation and coagulation than for the oxidation-dominated process. The influences of all other molecular descriptors on the synergistic process were weaker than on the oxidation-dominated process. PMID:27155432
NASA Astrophysics Data System (ADS)
Lee, Sanghun; Park, Sung Soo
2013-01-01
Using non-polarizable and polarizable molecular dynamics simulations, binary mixtures of propylene carbonate + dimethyl carbonate and propylene carbonate + ethylene carbonate with various compositions were investigated. The polarizable model produces more reasonable estimation of dielectric constants than the non-polarizable model; however, combining the electronic continuum model with the non-polarizable MD improves the comparison between the two models. Fair agreement was found between the results from these simulations and available experimental data. In addition, for a better understanding of the mixing behaviour, the excess dielectric constants over the entire composition were calculated. By comparison of the two mixtures in various mole fractions, distinctive mixing behaviours of propylene carbonate + dimethyl carbonate (poorly symmetric mixture) and propylene carbonate + ethylene carbonate (highly symmetric mixture) were observed.
Scurlock, R.D.; Ogilby, P.R.
1987-08-13
Relative rate constants for the radiative deactivation (k/sub r/) of singlet molecular oxygen (/sup 3/Sigma/sub g//sup -/O/sub 2/ reverse arrow /sup 1/..delta../sub g/O/sub 2/) have been determined in 15 solvents. A substantial solvent effect is observed. Changes in the value of k/sub r/ can exceed a factor of 20. A reasonably good correlation exists between the solvent polarizability, defined as a function of the solvent refractive index, and the radiative rate constant. We suggest that our data support a model in which /sup 1/..delta../sub g/O/sub 2/ is perturbed through the formation of a discrete oxygen-solvent collision complex.
Zhang, Peili; Wang, Mei; Yang, Yong; Yao, Tianyi; Sun, Licheng
2014-12-01
The copper complex [(bztpen)Cu](BF4)2 (bztpen=N-benzyl-N,N',N'-tris(pyridin-2-ylmethyl)ethylenediamine) displays high catalytic activity for electrochemical proton reduction in acidic aqueous solutions, with a calculated hydrogen-generation rate constant (k(obs)) of over 10000 s(-1). A turnover frequency (TOF) of 7000 h(-1) cm(-2) and a Faradaic efficiency of 96% were obtained from a controlled potential electrolysis (CPE) experiment with [(bztpen)Cu](2+) in pH 2.5 buffer solution at -0.90 V versus the standard hydrogen electrode (SHE) over two hours using a glassy carbon electrode. A mechanism involving two proton-coupled reduction steps was proposed for the dihydrogen generation reaction catalyzed by [(bztpen)Cu](2+). PMID:25314646
Upper limit on the rate constant for isotope exchange between molecular oxygen and ozone at 298 K
NASA Technical Reports Server (NTRS)
Anderson, S. M.; Morton, J.; Mauersberger, K.
1987-01-01
The gas phase bimolecular isotope exchange reaction between molecular oxygen and ozone has been investigated directly for the first time. Its rate coefficient is found to be less than 2 x 10 to the -25th cu cm/sec at 298 K, over six orders of magnitude below recent estimates. Much faster exchange was observed over condensed ozone at 77 K, suggesting isotopic scrambling is catalyzed under these conditions. The low rate coefficient implies that homogeneous exchange between ground state oxygen and ozone molecules cannot play a significant role in heavy ozone chemistry.
Rosskopf, Joachim; Paul-Yuan, Korbinian; Plenio, Martin B; Michaelis, Jens
2016-08-01
Analyzing the physical and chemical properties of single DNA-based molecular machines such as polymerases and helicases requires to track stepping motion on the length scale of base pairs. Although high-resolution instruments have been developed that are capable of reaching that limit, individual steps are oftentimes hidden by experimental noise which complicates data processing. Here we present an effective two-step algorithm which detects steps in a high-bandwidth signal by minimizing an energy-based model (energy-based step finder, EBS). First, an efficient convex denoising scheme is applied which allows compression to tuples of amplitudes and plateau lengths. Second, a combinatorial clustering algorithm formulated on a graph is used to assign steps to the tuple data while accounting for prior information. Performance of the algorithm was tested on Poissonian stepping data simulated based on published kinetics data of RNA polymerase II (pol II). Comparison to existing step-finding methods shows that EBS is superior in speed while providing competitive step-detection results, especially in challenging situations. Moreover, the capability to detect backtracked intervals in experimental data of pol II as well as to detect stepping behavior of the Phi29 DNA packaging motor is demonstrated. PMID:27627346
Fukuda, Ikuo; Kamiya, Narutoshi; Yonezawa, Yasushige; Nakamura, Haruki
2012-08-01
The zero-dipole summation method was extended to general molecular systems, and then applied to molecular dynamics simulations of an isotropic water system. In our previous paper [I. Fukuda, Y. Yonezawa, and H. Nakamura, J. Chem. Phys. 134, 164107 (2011)], for evaluating the electrostatic energy of a classical particle system, we proposed the zero-dipole summation method, which conceptually prevents the nonzero-charge and nonzero-dipole states artificially generated by a simple cutoff truncation. Here, we consider the application of this scheme to molecular systems, as well as some fundamental aspects of general cutoff truncation protocols. Introducing an idea to harmonize the bonding interactions and the electrostatic interactions in the scheme, we develop a specific algorithm. As in the previous study, the resulting energy formula is represented by a simple pairwise function sum, enabling facile applications to high-performance computation. The accuracy of the electrostatic energies calculated by the zero-dipole summation method with the atom-based cutoff was numerically investigated, by comparison with those generated by the Ewald method. We obtained an electrostatic energy error of less than 0.01% at a cutoff length longer than 13 Å for a TIP3P isotropic water system, and the errors were quite small, as compared to those obtained by conventional truncation methods. The static property and the stability in an MD simulation were also satisfactory. In addition, the dielectric constants and the distance-dependent Kirkwood factors were measured, and their coincidences with those calculated by the particle mesh Ewald method were confirmed, although such coincidences are not easily attained by truncation methods. We found that the zero damping-factor gave the best results in a practical cutoff distance region. In fact, in contrast to the zero-charge scheme, the damping effect was insensitive in the zero-charge and zero-dipole scheme, in the molecular system we
NASA Technical Reports Server (NTRS)
Vidal, C. R.; Stwalley, W. C.
1982-01-01
The molecular constants and their adiabatic corrections have been determined for the (A 1 Sigma +) - (X 1 Sigma +) system of the isotopic lithium hydrides: (Li-6)H, (Li-7)H, (Li-6)D, and (Li-7)D. Using a fully quantum mechanical variational method, the potential energy curves (IPA potentials) are determined. Extending the variational method, we have obtained for the first time adiabatic corrections of potential energy curves from isotopic spectroscopic data. A significant difference between the potential energy curves of the lithium hydrides and the lithium deuterides has been observed. When Li-6 was replaced by Li-7, a significant difference was only observed for the (A 1 Sigma +) state, but not for the (X 1 Sigma +) state.
Willow, Soohaeng Yoo; Salim, Michael A; Kim, Kwang S; Hirata, So
2015-01-01
A direct, simultaneous calculation of properties of a liquid using an ab initio electron-correlated theory has long been unthinkable. Here we present structural, dynamical, and response properties of liquid water calculated by ab initio molecular dynamics using the embedded-fragment spin-component-scaled second-order many-body perturbation method with the aug-cc-pVDZ basis set. This level of theory is chosen as it accurately and inexpensively reproduces the water dimer potential energy surface from the coupled-cluster singles, doubles, and noniterative triples with the aug-cc-pVQZ basis set, which is nearly exact. The calculated radial distribution function, self-diffusion coefficient, coordinate number, and dipole moment, as well as the infrared and Raman spectra are in excellent agreement with experimental results. The shapes and widths of the OH stretching bands in the infrared and Raman spectra and their isotropic-anisotropic Raman noncoincidence, which reflect the diverse local hydrogen-bond environment, are also reproduced computationally. The simulation also reveals intriguing dynamic features of the environment, which are difficult to probe experimentally, such as a surprisingly large fluctuation in the coordination number and the detailed mechanism by which the hydrogen donating water molecules move across the first and second shells, thereby causing this fluctuation. PMID:26400690
Friesner, Richard A.; Baik, Mu-Hyun; Gherman, Benjamin F.; Guallar, Victor; Wirstam, Maria E.; Murphy, Robert B.; Lippard, Stephen J.
2003-03-01
Over the past several years, rapid advances in computational hardware, quantum chemical methods, and mixed quantum mechanics/molecular mechanics (QM/MM) techniques have made it possible to model accurately the interaction of ligands with metal-containing proteins at an atomic level of detail. In this paper, we describe the application of our computational methodology, based on density functional (DFT) quantum chemical methods, to two diiron-containing proteins that interact with dioxygen: methane monooxygenase (MMO) and hemerythrin (Hr). Although the active sites are structurally related, the biological function differs substantially. MMO is an enzyme found in methanotrophic bacteria and hydroxylates aliphatic C-H bonds, whereas Hr is a carrier protein for dioxygen used by a number of marine invertebrates. Quantitative descriptions of the structures and energetics of key intermediates and transition states involved in the reaction with dioxygen are provided, allowing their mechanisms to be compared and contrasted in detail. An in-depth understanding of how the chemical identity of the first ligand coordination shell, structural features, electrostatic and van der Waals interactions of more distant shells control ligand binding and reactive chemistry is provided, affording a systematic analysis of how iron-containing proteins process dioxygen. Extensive contact with experiment is made in both systems, and a remarkable degree of accuracy and robustness of the calculations is obtained from both a qualitative and quantitative perspective.
NASA Astrophysics Data System (ADS)
Meng, Qingyong; Chen, Jun; Zhang, Dong H.
2016-04-01
To fast and accurately compute rate coefficients of the H/D + CH4 → H2/HD + CH3 reactions, we propose a segmented strategy for fitting suitable potential energy surface (PES), on which ring-polymer molecular dynamics (RPMD) simulations are performed. On the basis of recently developed permutation invariant polynomial neural-network approach [J. Li et al., J. Chem. Phys. 142, 204302 (2015)], PESs in local configuration spaces are constructed. In this strategy, global PES is divided into three parts, including asymptotic, intermediate, and interaction parts, along the reaction coordinate. Since less fitting parameters are involved in the local PESs, the computational efficiency for operating the PES routine is largely enhanced by a factor of ˜20, comparing with that for global PES. On interaction part, the RPMD computational time for the transmission coefficient can be further efficiently reduced by cutting off the redundant part of the child trajectories. For H + CH4, good agreements among the present RPMD rates and those from previous simulations as well as experimental results are found. For D + CH4, on the other hand, qualitative agreement between present RPMD and experimental results is predicted.
Willow, Soohaeng Yoo; Salim, Michael A.; Kim, Kwang S.; Hirata, So
2015-01-01
A direct, simultaneous calculation of properties of a liquid using an ab initio electron-correlated theory has long been unthinkable. Here we present structural, dynamical, and response properties of liquid water calculated by ab initio molecular dynamics using the embedded-fragment spin-component-scaled second-order many-body perturbation method with the aug-cc-pVDZ basis set. This level of theory is chosen as it accurately and inexpensively reproduces the water dimer potential energy surface from the coupled-cluster singles, doubles, and noniterative triples with the aug-cc-pVQZ basis set, which is nearly exact. The calculated radial distribution function, self-diffusion coefficient, coordinate number, and dipole moment, as well as the infrared and Raman spectra are in excellent agreement with experimental results. The shapes and widths of the OH stretching bands in the infrared and Raman spectra and their isotropic-anisotropic Raman noncoincidence, which reflect the diverse local hydrogen-bond environment, are also reproduced computationally. The simulation also reveals intriguing dynamic features of the environment, which are difficult to probe experimentally, such as a surprisingly large fluctuation in the coordination number and the detailed mechanism by which the hydrogen donating water molecules move across the first and second shells, thereby causing this fluctuation. PMID:26400690
Accurate far-infrared rotational frequencies of carbon monoxide
NASA Technical Reports Server (NTRS)
Varberg, Thomas D.; Evenson, Kenneth M.
1992-01-01
This study presents high-resolution measurements of the pure rotational absorption spectrum of CO in its ground state for the range J arcsec - 5-37. A least-squares fit to this data set, augmented by previous microwave measurements of the J arcsec = 0-4 rotational transitions in the literature, determined accurate values for the molecular constants. A table of calculated CO rotational frequencies is provided for the range J arcsec = 0-45.
Fahrenholz, Timothy; Wolle, Mesay Mulugeta; Kingston, H M Skip; Faber, Scott; Kern, John C; Pamuku, Matt; Miller, Logan; Chatragadda, Hemasudha; Kogelnik, Andreas
2015-01-20
Novel protocols were developed to accurately quantify reduced (GSH), oxidized (GSSG) and total (tGSH) glutathione in biological samples using molecular speciated isotope dilution mass spectrometry (SIDMS). For GSH and GSSG measurement, the sample was spiked with isotopically enriched analogues of the analytes ((310)GSH and (616)GSSG), along with N-ethylmaleimide (NEM), and treated with acetonitrile to solubilize the endogenous analytes via protein precipitation and equilibrate them with the spikes. The supernatant was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the analytes were quantified with simultaneous tracking and correction for auto-oxidation of GSH to GSSG. For tGSH assay, a (310)GSH-spiked sample was treated with dithiothreitol (DTT) to convert disulfide-bonded glutathione to GSH. After removing the protein, the supernatant was analyzed by LC-MS/MS and the analyte was quantified by single-spiking isotope dilution mass spectrometry (IDMS). The mathematical relationships in IDMS and SIDMS quantifications are based on isotopic ratios and do not involve calibration curves. The protocols were validated using spike recovery tests and by analyzing synthetic standard solutions. Red blood cell (RBC) and saliva samples obtained from healthy subjects, and whole blood samples collected and shipped from a remote location were analyzed. The concentrations of tGSH in the RBC and whole blood samples were 2 orders of magnitude higher than those found in saliva. The fractions of GSSG were 0.2-2.2% (RBC and blood) and 15-47% (saliva) of the free glutathione (GSH + 2xGSSG) in the corresponding samples. Up to 3% GSH was auto-oxidized to GSSG during sample workup; the highest oxidations (>1%) were in the saliva samples. PMID:25519489
Shi, Deheng; Li, Wentao; Sun, Jinfeng; Zhu, Zunlue
2012-02-15
The potential energy curves (PECs) of the X(1)Σ(+), a(3)Σ(+), A(1)Π and C(1)Σ(-) electronic states of the SiO molecule are studied using an ab initio quantum chemical method. The calculations have been made employing the complete active space self-consistent field (CASSCF) method, which is followed by the valence internally contracted multireference configuration interaction (MRCI) approach in combination with several correlation-consistent basis sets. The effect on the PECs by the core-valence correlation and relativistic corrections is included. The way to consider the relativistic correction is to use the third-order Douglas-Kroll Hamiltonian approximation. The core-valence correlation correction is carried out with the cc-pCVQZ basis set, and the relativistic correction is performed at the level of the cc-pVQZ basis set. To obtain more reliable results, the PECs determined by the MRCI calculations are also corrected for size-extensivity errors by means of the Davidson modification (MRCI+Q). The PECs of these electronic states are extrapolated to the complete basis set limit by the total-energy extrapolation scheme. Employing these PECs, the spectroscopic parameters are calculated and compared with those reported in the literature. With these PECs determined by the MRCI+Q/CV+DK+56 calculations, by solving the radial Schrödinger equation of nuclear motion, 110 vibrational states for the X(1)Σ(+), 69 for the a(3)Σ(+), 54 for the A(1)Π and 67 for the C(1)Σ(-) electronic state are predicted when the rotational quantum number J equals zero. The vibrational manifolds of the first 20 vibrational states are reported and compared with the available RKR data for each electronic state. On the whole, as expected, the most accurate spectroscopic parameters and molecular constants of the SiO molecule are obtained by the MRCI+Q/CV+DK+56 calculations. And the present molecular constants of the a(3)Σ(+), C(1)Σ(-) and A(1)Π electronic states determined by the MRCI
Chen, Qinghai; Wu, Nan; Xie, Meng; Zhang, Bo; Chen, Ming; Li, Jianjun; Zhuo, Lisha; Kuang, Hong; Fu, Weiling
2012-01-01
Summary The accurate and high-throughput detection of drug resistance-related multiple point mutations remains a challenge. Although the combination of molecular beacons with bio-immobilization technology, such as microarray, is promising, its application is difficult due to the ineffective immobilization of molecular beacons on the chip surface. Here, we propose a novel asymmetric-loop molecular beacon in which the loop consists of 2 parts. One is complementary to a target, while the other is complementary to an oligonucleotide probe immobilized on the chip surface. With this novel probe, a two-phase hybridization assay can be used for simultaneously detecting multiple point mutations. This assay will have advantages, such as easy probe availability, multiplex detection, low background, and high-efficiency hybridization, and may provide a new avenue for the immobilization of molecular beacons and high-throughput detection of point mutations. PMID:22460100
Formulas for determining rotational constants
NASA Astrophysics Data System (ADS)
Guelachvili, G.
This document is part of Subvolume B `Linear Triatomic Molecules', Part 9, of Volume 20 `Molecular Constants mostly from Infrared Spectroscopy' of Landolt-Börnstein Group II `Molecules and Radicals'. Part of the introduction, it states formulas for determining rotational constants, band center, band origin, and quadrupole coupling. Specific comments relate to BHO (HBO) and COS (OCS).
On the importance of having accurate data for astrophysical modelling
NASA Astrophysics Data System (ADS)
Lique, Francois
2016-06-01
The Herschel telescope and the ALMA and NOEMA interferometers have opened new windows of observation for wavelengths ranging from far infrared to sub-millimeter with spatial and spectral resolutions previously unmatched. To make the most of these observations, an accurate knowledge of the physical and chemical processes occurring in the interstellar and circumstellar media is essential.In this presentation, I will discuss what are the current needs of astrophysics in terms of molecular data and I will show that accurate molecular data are crucial for the proper determination of the physical conditions in molecular clouds.First, I will focus on collisional excitation studies that are needed for molecular lines modelling beyond the Local Thermodynamic Equilibrium (LTE) approach. In particular, I will show how new collisional data for the HCN and HNC isomers, two tracers of star forming conditions, have allowed solving the problem of their respective abundance in cold molecular clouds. I will also present the last collisional data that have been computed in order to analyse new highly resolved observations provided by the ALMA interferometer.Then, I will present the calculation of accurate rate constants for the F+H2 → HF+H and Cl+H2 ↔ HCl+H reactions, which have allowed a more accurate determination of the physical conditions in diffuse molecular clouds. I will also present the recent work on the ortho-para-H2 conversion due to hydrogen exchange that allow more accurate determination of the ortho-to-para-H2 ratio in the universe and that imply a significant revision of the cooling mechanism in astrophysical media.
Accurate quantum chemical calculations
NASA Technical Reports Server (NTRS)
Bauschlicher, Charles W., Jr.; Langhoff, Stephen R.; Taylor, Peter R.
1989-01-01
An important goal of quantum chemical calculations is to provide an understanding of chemical bonding and molecular electronic structure. A second goal, the prediction of energy differences to chemical accuracy, has been much harder to attain. First, the computational resources required to achieve such accuracy are very large, and second, it is not straightforward to demonstrate that an apparently accurate result, in terms of agreement with experiment, does not result from a cancellation of errors. Recent advances in electronic structure methodology, coupled with the power of vector supercomputers, have made it possible to solve a number of electronic structure problems exactly using the full configuration interaction (FCI) method within a subspace of the complete Hilbert space. These exact results can be used to benchmark approximate techniques that are applicable to a wider range of chemical and physical problems. The methodology of many-electron quantum chemistry is reviewed. Methods are considered in detail for performing FCI calculations. The application of FCI methods to several three-electron problems in molecular physics are discussed. A number of benchmark applications of FCI wave functions are described. Atomic basis sets and the development of improved methods for handling very large basis sets are discussed: these are then applied to a number of chemical and spectroscopic problems; to transition metals; and to problems involving potential energy surfaces. Although the experiences described give considerable grounds for optimism about the general ability to perform accurate calculations, there are several problems that have proved less tractable, at least with current computer resources, and these and possible solutions are discussed.
Connecting Fundamental Constants
Di Mario, D.
2008-05-29
A model for a black hole electron is built from three basic constants only: h, c and G. The result is a description of the electron with its mass and charge. The nature of this black hole seems to fit the properties of the Planck particle and new relationships among basic constants are possible. The time dilation factor in a black hole associated with a variable gravitational field would appear to us as a charge; on the other hand the Planck time is acting as a time gap drastically limiting what we are able to measure and its dimension will appear in some quantities. This is why the Planck time is numerically very close to the gravitational/electric force ratio in an electron: its difference, disregarding a {pi}{radical}(2) factor, is only 0.2%. This is not a coincidence, it is always the same particle and the small difference is between a rotating and a non-rotating particle. The determination of its rotational speed yields accurate numbers for many quantities, including the fine structure constant and the electron magnetic moment.
NASA Astrophysics Data System (ADS)
Kapil, V.; VandeVondele, J.; Ceriotti, M.
2016-02-01
The development and implementation of increasingly accurate methods for electronic structure calculations mean that, for many atomistic simulation problems, treating light nuclei as classical particles is now one of the most serious approximations. Even though recent developments have significantly reduced the overhead for modeling the quantum nature of the nuclei, the cost is still prohibitive when combined with advanced electronic structure methods. Here we present how multiple time step integrators can be combined with ring-polymer contraction techniques (effectively, multiple time stepping in imaginary time) to reduce virtually to zero the overhead of modelling nuclear quantum effects, while describing inter-atomic forces at high levels of electronic structure theory. This is demonstrated for a combination of MP2 and semi-local DFT applied to the Zundel cation. The approach can be seamlessly combined with other methods to reduce the computational cost of path integral calculations, such as high-order factorizations of the Boltzmann operator or generalized Langevin equation thermostats.
NASA Astrophysics Data System (ADS)
Charanya, Tauseef; York, Timothy; Bloch, Sharon; Sudlow, Gail; Liang, Kexian; Garcia, Missael; Akers, Walter J.; Rubin, Deborah; Gruev, Viktor; Achilefu, Samuel
2014-12-01
Colitis-associated cancer (CAC) arises from premalignant flat lesions of the colon, which are difficult to detect with current endoscopic screening approaches. We have developed a complementary fluorescence and polarization reporting strategy that combines the unique biochemical and physical properties of dysplasia and cancer for real-time detection of these lesions. Using azoxymethane-dextran sodium sulfate (AOM-DSS) treated mice, which recapitulates human CAC and dysplasia, we show that an octapeptide labeled with a near-infrared (NIR) fluorescent dye selectively identified all precancerous and cancerous lesions. A new thermoresponsive sol-gel formulation allowed topical application of the molecular probe during endoscopy. This method yielded high contrast-to-noise ratios (CNR) between adenomatous tumors (20.6±1.65) and flat lesions (12.1±1.03) and surrounding uninvolved colon tissue versus CNR of inflamed tissues (1.62±0.41). Incorporation of nanowire-filtered polarization imaging into NIR fluorescence endoscopy shows a high depolarization contrast in both adenomatous tumors and flat lesions in CAC, reflecting compromised structural integrity of these tissues. Together, the real-time polarization imaging provides real-time validation of suspicious colon tissue highlighted by molecular fluorescence endoscopy.
Charanya, Tauseef; York, Timothy; Bloch, Sharon; Sudlow, Gail; Liang, Kexian; Garcia, Missael; Akers, Walter J.; Rubin, Deborah; Gruev, Viktor; Achilefu, Samuel
2014-01-01
Abstract. Colitis-associated cancer (CAC) arises from premalignant flat lesions of the colon, which are difficult to detect with current endoscopic screening approaches. We have developed a complementary fluorescence and polarization reporting strategy that combines the unique biochemical and physical properties of dysplasia and cancer for real-time detection of these lesions. Using azoxymethane-dextran sodium sulfate (AOM-DSS) treated mice, which recapitulates human CAC and dysplasia, we show that an octapeptide labeled with a near-infrared (NIR) fluorescent dye selectively identified all precancerous and cancerous lesions. A new thermoresponsive sol-gel formulation allowed topical application of the molecular probe during endoscopy. This method yielded high contrast-to-noise ratios (CNR) between adenomatous tumors (20.6±1.65) and flat lesions (12.1±1.03) and surrounding uninvolved colon tissue versus CNR of inflamed tissues (1.62±0.41). Incorporation of nanowire-filtered polarization imaging into NIR fluorescence endoscopy shows a high depolarization contrast in both adenomatous tumors and flat lesions in CAC, reflecting compromised structural integrity of these tissues. Together, the real-time polarization imaging provides real-time validation of suspicious colon tissue highlighted by molecular fluorescence endoscopy. PMID:25473883
Kapil, V; VandeVondele, J; Ceriotti, M
2016-02-01
The development and implementation of increasingly accurate methods for electronic structure calculations mean that, for many atomistic simulation problems, treating light nuclei as classical particles is now one of the most serious approximations. Even though recent developments have significantly reduced the overhead for modeling the quantum nature of the nuclei, the cost is still prohibitive when combined with advanced electronic structure methods. Here we present how multiple time step integrators can be combined with ring-polymer contraction techniques (effectively, multiple time stepping in imaginary time) to reduce virtually to zero the overhead of modelling nuclear quantum effects, while describing inter-atomic forces at high levels of electronic structure theory. This is demonstrated for a combination of MP2 and semi-local DFT applied to the Zundel cation. The approach can be seamlessly combined with other methods to reduce the computational cost of path integral calculations, such as high-order factorizations of the Boltzmann operator or generalized Langevin equation thermostats. PMID:26851912
Poutsma, Marvin L
2012-01-01
Rate constants for the reaction (R 3C + X2 R 3CX + X ; X = F, Cl, Br, and I) are reviewed. Because of curved Arrhenius plots and negative EX values, empirical structure-reactivity correlations are sought for log kX,298 rather than EX. The well-known poor correlation with measures of reaction enthalpy is demonstrated. The best quantitative predictor for R 3C is p, the sum of the Hammett p constants for the three substituents, R . Electronegative substituents with lone pairs, such as halogen or oxygen, thus appear to destabilize the formation of a polarized pre-reaction complex and/or TS ( +R---X---X -) by -inductive/field electron withdrawal while simultaneously stabilizing them by -resonance electron donation. The best quantitative predictor of the reactivity order of the halogens, I2 > Br2 >> Cl2 F2, is the polarizability of the halogen, (X-X). For the data set of 60 rate constants which span 6.5 orders of magnitude, a modestly successful correlation of log kX,298 is achieved with only two parameters, p and (X-X), with a mean unsigned deviation of 0.59 log units. How much of this residual variance is the result of inaccuracies in the data compared with over-simplification of the correlation approach remains to be seen.
Le, Hung M; Dinh, Thach S; Le, Hieu V
2011-10-13
The singlet-triplet transformation and molecular dissociation of ozone (O(3)) gas is investigated by performing quasi-classical molecular dynamics (MD) simulations on an ab initio potential energy surface (PES) with visible and near-infrared excitations. MP4(SDQ) level of theory with the 6-311g(2d,2p) basis set is executed for three different electronic spin states (singlet, triplet, and quintet). In order to simplify the potential energy function, an approximation is adopted by ignoring the spin-orbit coupling and allowing the molecule to switch favorably and instantaneously to the spin state that is more energetically stable (lowest in energy among the three spin states). This assumption has previously been utilized to study the SiO(2) system as reported by Agrawal et al. (J. Chem. Phys. 2006, 124 (13), 134306). The use of such assumption in this study probably makes the upper limits of computed rate coefficients the true rate coefficients. The global PES for ozone is constructed by fitting 5906 ab initio data points using a 60-neuron two-layer feed-forward neural network. The mean-absolute error and root-mean-squared error of this fit are 0.0446 eV (1.03 kcal/mol) and 0.0756 eV (1.74 kcal/mol), respectively, which reveal very good fitting accuracy. The parameter coefficients of the global PES are reported in this paper. In order to identify the spin state with high confidence, we propose the use of a pattern-recognition neural network, which is trained to predict the spin state of a given configuration (with a prediction accuracy being 95.6% on a set of testing data points). To enhance the prediction effectiveness, a buffer series of five points are validated to confirm the spin state during the MD process to gain better confidence. Quasi-classical MD simulations from 1.2 to 2.4 eV of total internal energy (including zero-point energy) result in rate coefficients of singlet-triplet transformation in the range of 0.027 ps(-1) to 1.21 ps(-1). Also, we find very
Tully, R B
1993-06-01
Five methods of estimating distances have demonstrated internal reproducibility at the level of 5-20% rms accuracy. The best of these are the cepheid (and RR Lyrae), planetary nebulae, and surface-brightness fluctuation techniques. Luminosity-line width and Dn-sigma methods are less accurate for an individual case but can be applied to large numbers of galaxies. The agreement is excellent between these five procedures. It is determined that Hubble constant H0 = 90 +/- 10 km.s-1.Mpc-1 [1 parsec (pc) = 3.09 x 10(16) m]. It is difficult to reconcile this value with the preferred world model even in the low-density case. The standard model with Omega = 1 may be excluded unless there is something totally misunderstood about the foundation of the distance scale or the ages of stars. PMID:11607391
Tully, R B
1993-01-01
Five methods of estimating distances have demonstrated internal reproducibility at the level of 5-20% rms accuracy. The best of these are the cepheid (and RR Lyrae), planetary nebulae, and surface-brightness fluctuation techniques. Luminosity-line width and Dn-sigma methods are less accurate for an individual case but can be applied to large numbers of galaxies. The agreement is excellent between these five procedures. It is determined that Hubble constant H0 = 90 +/- 10 km.s-1.Mpc-1 [1 parsec (pc) = 3.09 x 10(16) m]. It is difficult to reconcile this value with the preferred world model even in the low-density case. The standard model with Omega = 1 may be excluded unless there is something totally misunderstood about the foundation of the distance scale or the ages of stars. PMID:11607391
Deshpande, Amol A; Madhavan, P; Deshpande, Girish R; Chandel, Ravi Kumar; Yarbagi, Kaviraj M; Joshi, Alok R; Moses Babu, J; Murali Krishna, R; Rao, I M
2016-01-01
Fondaparinux sodium is a synthetic low-molecular-weight heparin (LMWH). This medication is an anticoagulant or a blood thinner, prescribed for the treatment of pulmonary embolism and prevention and treatment of deep vein thrombosis. Its determination in the presence of related impurities was studied and validated by a novel ion-pair HPLC method. The separation of the drug and its degradation products was achieved with the polymer-based PLRPs column (250 mm × 4.6 mm; 5 μm) in gradient elution mode. The mixture of 100 mM n-hexylamine and 100 mM acetic acid in water was used as buffer solution. Mobile phase A and mobile phase B were prepared by mixing the buffer and acetonitrile in the ratio of 90:10 (v/v) and 20:80 (v/v), respectively. Mobile phases were delivered in isocratic mode (2% B for 0-5 min) followed by gradient mode (2-85% B in 5-60 min). An Evaporative Light Scattering Detector (ELSD) was connected to the LC system to detect the responses of chromatographic separation. Further, the drug was subjected to stress studies for acidic, basic, oxidative, photolytic, and thermal degradations as per ICH guidelines and the drug was found to be labile in acid, base hydrolysis, and oxidation, while stable in neutral, thermal, and photolytic degradation conditions. The method provided linear responses over the concentration range of the LOQ to 0.30% for each impurity with respect to the analyte concentration of 12.5 mg/mL, and regression analysis showed a correlation coefficient value (r(2)) of more than 0.99 for all the impurities. The LOD and LOQ were found to be 1.4 µg/mL and 4.1 µg/mL, respectively, for fondaparinux. The developed ion-pair method was validated as per ICH guidelines with respect to accuracy, selectivity, precision, linearity, and robustness. PMID:27110496
Deshpande, Amol A.; Madhavan, P.; Deshpande, Girish R.; Chandel, Ravi Kumar; Yarbagi, Kaviraj M.; Joshi, Alok R.; Moses Babu, J.; Murali Krishna, R.; Rao, I. M.
2016-01-01
Fondaparinux sodium is a synthetic low-molecular-weight heparin (LMWH). This medication is an anticoagulant or a blood thinner, prescribed for the treatment of pulmonary embolism and prevention and treatment of deep vein thrombosis. Its determination in the presence of related impurities was studied and validated by a novel ion-pair HPLC method. The separation of the drug and its degradation products was achieved with the polymer-based PLRPs column (250 mm × 4.6 mm; 5 μm) in gradient elution mode. The mixture of 100 mM n-hexylamine and 100 mM acetic acid in water was used as buffer solution. Mobile phase A and mobile phase B were prepared by mixing the buffer and acetonitrile in the ratio of 90:10 (v/v) and 20:80 (v/v), respectively. Mobile phases were delivered in isocratic mode (2% B for 0–5 min) followed by gradient mode (2–85% B in 5–60 min). An Evaporative Light Scattering Detector (ELSD) was connected to the LC system to detect the responses of chromatographic separation. Further, the drug was subjected to stress studies for acidic, basic, oxidative, photolytic, and thermal degradations as per ICH guidelines and the drug was found to be labile in acid, base hydrolysis, and oxidation, while stable in neutral, thermal, and photolytic degradation conditions. The method provided linear responses over the concentration range of the LOQ to 0.30% for each impurity with respect to the analyte concentration of 12.5 mg/mL, and regression analysis showed a correlation coefficient value (r2) of more than 0.99 for all the impurities. The LOD and LOQ were found to be 1.4 µg/mL and 4.1 µg/mL, respectively, for fondaparinux. The developed ion-pair method was validated as per ICH guidelines with respect to accuracy, selectivity, precision, linearity, and robustness. PMID:27110496
NASA Technical Reports Server (NTRS)
Jaffee, R. L.
1978-01-01
Classical trajectory calculations are presented for the reaction ClO + O yields Cl + O2, a reaction which is an important step in the chlorine-catalyzed destruction of ozone which is thought to occur in the 220 and 1000 K. The calculated rate constant is 4.36 x 10 to the minus 11th power exp (-191/T)cu cm molecule (-1)s(-1) and its value at 300 K is 2.3 plus or minus 10 to the 11th power cu cm molecule (-1)s(-1), about a factor of 2 lower than recent experimental data. The empirical potential energy surface used in the calculations was constructed to fit experimental data for ClO, O2 and ClOO molecules. Other important features of this potential surface, such as the barrier to reaction, were varied systematically and calculations were performed for a range of conditions to determine the best theoretical rate constants. Results demonstrate the utility of classical trajectory methods for determining activation energies and other kinetic data for important atmospheric reactions.
NASA Astrophysics Data System (ADS)
Chakraborty, Arindam; Zhao, Yan; Lin, Hai; Truhlar, Donald G.
2006-01-01
This article presents a multifaceted study of the reaction H +C2H6→H2+C2H5 and three of its deuterium-substituted isotopologs. First we present high-level electronic structure calculations by the W1, G3SX, MCG3-MPWB, CBS-APNO, and MC-QCISD/3 methods that lead to a best estimate of the barrier height of 11.8±0.5kcal/mol. Then we obtain a specific reaction parameter for the MPW density functional in order that it reproduces the best estimate of the barrier height; this yields the MPW54 functional. The MPW54 functional, as well as the MPW60 functional that was previously parametrized for the H +CH4 reaction, is used with canonical variational theory with small-curvature tunneling to calculate the rate constants for all four ethane reactions from 200 to 2000 K. The final MPW54 calculations are based on curvilinear-coordinate generalized-normal-mode analysis along the reaction path, and they include scaled frequencies and an anharmonic C-C bond torsion. They agree with experiment within 31% for 467-826 K except for a 38% deviation at 748 K; the results for the isotopologs are predictions since these rate constants have never been measured. The kinetic isotope effects (KIEs) are analyzed to reveal the contributions from subsets of vibrational partition functions and from tunneling, which conspire to yield a nonmonotonic temperature dependence for one of the KIEs. The stationary points and reaction-path potential of the MPW54 potential-energy surface are then used to parametrize a new kind of analytical potential-energy surface that combines a semiempirical valence bond formalism for the reactive part of the molecule with a standard molecular mechanics force field for the rest; this may be considered to be either an extension of molecular mechanics to treat a reactive potential-energy surface or a new kind of combined quantum-mechanical/molecular mechanical (QM/MM) method in which the QM part is semiempirical valence bond theory; that is, the new potential
NASA Astrophysics Data System (ADS)
Greives, Nicholas; Zhou, Huan-Xiang
2012-10-01
A method developed by Northrup et al. [J. Chem. Phys. 80, 1517 (1984)], 10.1063/1.446900 for calculating protein-ligand binding rate constants (ka) from Brownian dynamics (BD) simulations has been widely used for rigid molecules. Application to flexible molecules is limited by the formidable computational cost to treat conformational fluctuations during the long BD simulations necessary for ka calculation. Here, we propose a new method called BDflex for ka calculation that circumvents this problem. The basic idea is to separate the whole space into an outer region and an inner region, and formulate ka as the product of kE and bar η _d, which are obtained by separately solving exterior and interior problems. kE is the diffusion-controlled rate constant for the ligand in the outer region to reach the dividing surface between the outer and inner regions; in this exterior problem conformational fluctuations can be neglected. bar η _d is the probability that the ligand, starting from the dividing surface, will react at the binding site rather than escape to infinity. The crucial step in reducing the determination of bar η _d to a problem confined to the inner region is a radiation boundary condition imposed on the dividing surface; the reactivity on this boundary is proportional to kE. By confining the ligand to the inner region and imposing the radiation boundary condition, we avoid multiple-crossing of the dividing surface before reaction at the binding site and hence dramatically cut down the total simulation time, making the treatment of conformational fluctuations affordable. BDflex is expected to have wide applications in problems where conformational fluctuations of the molecules are crucial for productive ligand binding, such as in cases where transient widening of a bottleneck allows the ligand to access the binding pocket, or the binding site is properly formed only after ligand entrance induces the closure of a lid.
Accurate equilibrium structures of fluoro- and chloroderivatives of methane
NASA Astrophysics Data System (ADS)
Vogt, Natalja; Demaison, Jean; Rudolph, Heinz Dieter
2014-11-01
This work is a systematic study of molecular structure of fluoro-, chloro-, and fluorochloromethanes. For the first time, the accurate ab initio structure is computed for 10 molecules (CF4, CClF3, CCl2F2, CCl3F, CHClF2, CHCl2F, CH2F2, CH2ClF, CH2Cl2, and CCl4) at the coupled cluster level of electronic structure theory including single and double excitations augmented by a perturbational estimate of the effects of connected triple excitations [CCSD(T)] with all electrons being correlated and Gaussian basis sets of at least quadruple-ζ quality. Furthermore, when possible, namely for the molecules CH2F2, CH2Cl2, CH2ClF, CHClF2, and CCl2F2, accurate semi-experimental equilibrium (rSEe) structure has also been determined. This is achieved through a least-squares structural refinement procedure based on the equilibrium rotational constants of all available isotopomers, determined by correcting the experimental ground-state rotational constants with computed ab initio vibration-rotation interaction constants and electronic g-factors. The computed and semi-experimental equilibrium structures are in excellent agreement with each other, but the rSEe structure is generally more accurate, in particular for the CF and CCl bond lengths. The carbon-halogen bond length is discussed within the framework of the ligand close-packing model as a function of the atomic charges. For this purpose, the accurate equilibrium structures of some other molecules with alternative ligands, such as CH3Li, CF3CCH, and CF3CN, are also computed.
Kutateladze, Andrei G; Mukhina, Olga A
2014-09-01
Spin-spin coupling constants in (1)H NMR carry a wealth of structural information and offer a powerful tool for deciphering molecular structures. However, accurate ab initio or DFT calculations of spin-spin coupling constants have been very challenging and expensive. Scaling of (easy) Fermi contacts, fc, especially in the context of recent findings by Bally and Rablen (Bally, T.; Rablen, P. R. J. Org. Chem. 2011, 76, 4818), offers a framework for achieving practical evaluation of spin-spin coupling constants. We report a faster and more precise parametrization approach utilizing a new basis set for hydrogen atoms optimized in conjunction with (i) inexpensive B3LYP/6-31G(d) molecular geometries, (ii) inexpensive 4-31G basis set for carbon atoms in fc calculations, and (iii) individual parametrization for different atom types/hybridizations, not unlike a force field in molecular mechanics, but designed for the fc's. With the training set of 608 experimental constants we achieved rmsd <0.19 Hz. The methodology performs very well as we illustrate with a set of complex organic natural products, including strychnine (rmsd 0.19 Hz), morphine (rmsd 0.24 Hz), etc. This precision is achieved with much shorter computational times: accurate spin-spin coupling constants for the two conformers of strychnine were computed in parallel on two 16-core nodes of a Linux cluster within 10 min. PMID:25158224
Perdiguero, Pedro; Venturas, Martin; Cervera, María Teresa; Gil, Luis; Collada, Carmen
2015-01-01
Elms, especially Ulmus minor and U. americana, are carrying out a hard battle against Dutch elm disease (DED). This vascular wilt disease, caused by Ophiostoma ulmi and O. novo-ulmi, appeared in the twentieth century and killed millions of elms across North America and Europe. Elm breeding and conservation programmes have identified a reduced number of DED tolerant genotypes. In this study, three U. minor genotypes with contrasted levels of tolerance to DED were exposed to several biotic and abiotic stresses in order to (i) obtain a de novo assembled transcriptome of U. minor using 454 pyrosequencing, (ii) perform a functional annotation of the assembled transcriptome, (iii) identify genes potentially involved in the molecular response to environmental stress, and (iv) develop gene-based markers to support breeding programmes. A total of 58,429 putative unigenes were identified after assembly and filtering of the transcriptome. 32,152 of these unigenes showed homology with proteins identified in the genome from the most common plant model species. Well-known family proteins and transcription factors involved in abiotic, biotic or both stresses were identified after functional annotation. A total of 30,693 polymorphisms were identified in 7,125 isotigs, a large number of them corresponding to single nucleotide polymorphisms (SNPs; 27,359). In a subset randomly selected for validation, 87% of the SNPs were confirmed. The material generated may be valuable for future Ulmus gene expression, population genomics and association genetics studies, especially taking into account the scarce molecular information available for this genus and the great impact that DED has on elm populations. PMID:26257751
Perdiguero, Pedro; Venturas, Martin; Cervera, María Teresa; Gil, Luis; Collada, Carmen
2015-01-01
Elms, especially Ulmus minor and U. americana, are carrying out a hard battle against Dutch elm disease (DED). This vascular wilt disease, caused by Ophiostoma ulmi and O. novo-ulmi, appeared in the twentieth century and killed millions of elms across North America and Europe. Elm breeding and conservation programmes have identified a reduced number of DED tolerant genotypes. In this study, three U. minor genotypes with contrasted levels of tolerance to DED were exposed to several biotic and abiotic stresses in order to (i) obtain a de novo assembled transcriptome of U. minor using 454 pyrosequencing, (ii) perform a functional annotation of the assembled transcriptome, (iii) identify genes potentially involved in the molecular response to environmental stress, and (iv) develop gene-based markers to support breeding programmes. A total of 58,429 putative unigenes were identified after assembly and filtering of the transcriptome. 32,152 of these unigenes showed homology with proteins identified in the genome from the most common plant model species. Well-known family proteins and transcription factors involved in abiotic, biotic or both stresses were identified after functional annotation. A total of 30,693 polymorphisms were identified in 7,125 isotigs, a large number of them corresponding to single nucleotide polymorphisms (SNPs; 27,359). In a subset randomly selected for validation, 87% of the SNPs were confirmed. The material generated may be valuable for future Ulmus gene expression, population genomics and association genetics studies, especially taking into account the scarce molecular information available for this genus and the great impact that DED has on elm populations. PMID:26257751
Accurate Molecular Dimensions from Stearic Acid Monolayers.
ERIC Educational Resources Information Center
Lane, Charles A.; And Others
1984-01-01
Discusses modifications in the fatty acid monolayer experiment to reduce the inaccurate moleculary data students usually obtain. Copies of the experimental procedure used and a Pascal computer program to work up the data are available from the authors. (JN)
A priori predictions of the rotational constants for protonated formaldehyde and protonated methanol
NASA Technical Reports Server (NTRS)
Defrees, D. J.; Mclean, A. D.
1986-01-01
Protonated formaldehyde and protonated methanol are candidate interstellar molecules and models for classes of protonated oxygen compounds. Ab initio molecular orbital theory has been used to compute rotational constants to guide spectroscopic searches both in the laboratory and in space. The ab initio results are empirically correct to account for systematic deficiencies in the theory and zero-point vibrational effects; they are expected to be accurate to about + or - 2 percent. For H2COH(+) the resultant constants are (in GHz) A = 194.3, B = 34.28, and C = 29.14; for H3COH2(+) A = 103.7, B = 21.18, and C = 20.30.
NASA Astrophysics Data System (ADS)
Houriez, Céline; Ferré, Nicolas; Masella, Michel; Siri, Didier
2008-06-01
We present a combined theoretical approach based on analyzing molecular dynamics trajectories (at the nanosecond scale) generated by use of classical polarizable force fields and on quantum calculations to compute averaged hyperfine coupling constants. That method is used to estimate the constant of a prototypical nitroxide: the dimethylnitroxide. The molecule is embedded during the simulations in a cubic box containing about 500 water molecules and the molecular dynamics is generated using periodic conditions. Once the trajectories are achieved, the nitroxide and its first hydration shell molecules are extracted, and the coupling constants are computed by considering the latter aggregates by means of quantum computations. However, all the water molecules of the bulk are also accounted for during those computations by means of the electrostatic potential fitted method. Our results exhibit that in order to predict accurate and reliable coupling constants, one needs to describe carefully the out-of-plane motion of the nitroxide nitrogen and to sample trajectories with a time interval of 400 fs at least to generate an uncorrelated large set of nitroxide structures. Compared to Car-Parrinello molecular dynamics techniques, our approach can be used readily to compute hyperfine coupling constants of large systems, such as nitroxides of great size interacting with macromolecules such as proteins or polymers.
Houriez, Céline; Ferré, Nicolas; Masella, Michel; Siri, Didier
2008-06-28
We present a combined theoretical approach based on analyzing molecular dynamics trajectories (at the nanosecond scale) generated by use of classical polarizable force fields and on quantum calculations to compute averaged hyperfine coupling constants. That method is used to estimate the constant of a prototypical nitroxide: the dimethylnitroxide. The molecule is embedded during the simulations in a cubic box containing about 500 water molecules and the molecular dynamics is generated using periodic conditions. Once the trajectories are achieved, the nitroxide and its first hydration shell molecules are extracted, and the coupling constants are computed by considering the latter aggregates by means of quantum computations. However, all the water molecules of the bulk are also accounted for during those computations by means of the electrostatic potential fitted method. Our results exhibit that in order to predict accurate and reliable coupling constants, one needs to describe carefully the out-of-plane motion of the nitroxide nitrogen and to sample trajectories with a time interval of 400 fs at least to generate an uncorrelated large set of nitroxide structures. Compared to Car-Parrinello molecular dynamics techniques, our approach can be used readily to compute hyperfine coupling constants of large systems, such as nitroxides of great size interacting with macromolecules such as proteins or polymers. PMID:18601346
NASA Technical Reports Server (NTRS)
Bailey, David H.; Borwein, Jonathan M.; Crandall, Richard E.; Craw, James M. (Technical Monitor)
1995-01-01
We prove known identities for the Khinchin constant and develop new identities for the more general Hoelder mean limits of continued fractions. Any of these constants can be developed as a rapidly converging series involving values of the Riemann zeta function and rational coefficients. Such identities allow for efficient numerical evaluation of the relevant constants. We present free-parameter, optimizable versions of the identities, and report numerical results.
Solar constant secular changes
NASA Technical Reports Server (NTRS)
Schatten, Kenneth H.; Orosz, Jerome A.
1990-01-01
A recent model for solar constant secular changes is used to calculate a 'proxy' solar constant for: (1) the past four centuries, based upon the sunspot record, (2) the past nine centuries, based upon C-14 observations and their relation to solar activity, and (3) the next decade, based upon a dynamo theory model for the solar cycle. The proxy solar constant data is tabulated as it may be useful for climate modelers studying global climate changes.
Optical constants of concentrated aqueous ammonium sulfate.
NASA Technical Reports Server (NTRS)
Remsberg, E. E.
1973-01-01
Using experimental data obtained from applying spectroscopy to a 39-wt-% aqueous ammonium sulfate solution, it is shown that, even though specific aerosol optical constants appear quite accurate, spectral variations may exist as functions of material composition or concentration or both. Prudent users of optical constant data must then include liberal data error estimates when performing calculations or in interpreting spectroscopic surveys of collected aerosol material.
ERIC Educational Resources Information Center
Rom, Mark Carl
2011-01-01
Grades matter. College grading systems, however, are often ad hoc and prone to mistakes. This essay focuses on one factor that contributes to high-quality grading systems: grading accuracy (or "efficiency"). I proceed in several steps. First, I discuss the elements of "efficient" (i.e., accurate) grading. Next, I present analytical results…
NASA Astrophysics Data System (ADS)
1995-08-01
about the distances to galaxies and thereby about the expansion rate of the Universe. A simple way to determine the distance to a remote galaxy is by measuring its redshift, calculate its velocity from the redshift and divide this by the Hubble constant, H0. For instance, the measured redshift of the parent galaxy of SN 1995K (0.478) yields a velocity of 116,000 km/sec, somewhat more than one-third of the speed of light (300,000 km/sec). From the universal expansion rate, described by the Hubble constant (H0 = 20 km/sec per million lightyears as found by some studies), this velocity would indicate a distance to the supernova and its parent galaxy of about 5,800 million lightyears. The explosion of the supernova would thus have taken place 5,800 million years ago, i.e. about 1,000 million years before the solar system was formed. However, such a simple calculation works only for relatively ``nearby'' objects, perhaps out to some hundred million lightyears. When we look much further into space, we also look far back in time and it is not excluded that the universal expansion rate, i.e. the Hubble constant, may have been different at earlier epochs. This means that unless we know the change of the Hubble constant with time, we cannot determine reliable distances of distant galaxies from their measured redshifts and velocities. At the same time, knowledge about such change or lack of the same will provide unique information about the time elapsed since the Universe began to expand (the ``Big Bang''), that is, the age of the Universe and also its ultimate fate. The Deceleration Parameter q0 Cosmologists are therefore eager to determine not only the current expansion rate (i.e., the Hubble constant, H0) but also its possible change with time (known as the deceleration parameter, q0). Although a highly accurate value of H0 has still not become available, increasing attention is now given to the observational determination of the second parameter, cf. also the Appendix at the
Fundamental Physical Constants
National Institute of Standards and Technology Data Gateway
SRD 121 CODATA Fundamental Physical Constants (Web, free access) This site, developed in the Physics Laboratory at NIST, addresses three topics: fundamental physical constants, the International System of Units (SI), which is the modern metric system, and expressing the uncertainty of measurement results.
Wang, Ting; Yin, Hongyun; Wang, Dunyou; Valiev, Marat
2012-02-16
The bimolecular nucleophilic substitution reaction of CCl{sub 4} and OH{sup -} in aqueous solution was investigated on the basis of a combined quantum mechanical and molecular mechanics method. A multilayered representation approach is employed to achieve high accuracy results at the CCSD(T) level of theory. The potential of mean force calculations at the DFT level and CCSD(T) level of theory yield reaction barrier heights of 22.7 and 27.9 kcal/mol, respectively. Both the solvation effects and the solvent-induced polarization effect have significant contributions to the reaction energetics, for example, the solvation effect raises the saddle point by 10.6 kcal/mol. The calculated rate constant coefficient is 8.6 x 10{sup -28} cm{sup 3} molecule{sup -1} s{sup -1} at the standard state condition, which is about 17 orders magnitude smaller than that in the gas phase. Among the four chloromethanes (CH{sub 3}Cl, CH{sub 2}Cl{sub 2}, CHCl{sub 3}, and CCl{sub 4}), CCl{sub 4} has the lowest free energy activation barrier for the reaction with OH{sup -1} in aqueous solution, confirming the trend that substitution of Cl by H in chloromethanes diminishes the reactivity.
Tang, W-R; Shioya, N; Eguchi, T; Ebata, T; Matsui, J; Takenouchi, H; Honma, D; Yasue, H; Takagaki, Y; Enosawa, S; Itagaki, M; Taguchi, T; Kiyokawa, N; Amemiya, H; Fujimoto, J
2005-01-10
A battery of mouse monoclonal antibodies (mAbs) reactive with porcine peripheral blood (PB) leukocytes was generated. Among the mAbs, 6F10 was found to react probably with cluster of differentiation (CD)8 alpha-chain, while 7G3 and 3E12 were found to recognize gammadelta T-cells, as revealed by two-color flow cytometric and immunoprecipitation studies. 7G3 was shown to react with the constant (C) region of the T-cell receptor (TCR) delta-chain by the following facts: (1) 7G3 immunoprecipitated full-length TCR delta-chain protein fused with glutathione S-transferase (GST) produced by Esherichia coli and (2) 7G3 reacted with TCR delta-chain expressing Cos-7 cells transfected with either full-length or N-terminal deleted mutant cDNA, but did not react with Cos-7 cells transfected with C-terminal deleted mutant TCR delta-chain cDNA. All three mAbs produced high-quality immunostaining results on frozen sections, revealing a distinct distribution of gammadelta T-cells and CD8(+) cells. This report precisely characterizes mAbs against porcine TCR for the first time, facilitating molecular biological investigations of the porcine immune system. PMID:15626467
Experimental rovibrational constants and equilibrium structure of phosphorus trifluoride
NASA Astrophysics Data System (ADS)
Najib, Hamid
2014-11-01
Thanks to recent high-resolution Fourier transform infrared (FTIR) and pure rotational (RF/CM/MMW) measurements, several experimental values of the rotation-vibration parameters of the oblate molecule PF3 have been extracted, contributing thus to the knowledge of the molecular potential of phosphorus trifluoride. The data used are those of the fundamental, overtone and combination bands studied in the 300-1500 cm-1 range. The new values are in good agreement with ones determined at low resolution, but significantly more accurate. The agreement is excellent with the available values determined by ab initio HF-SCF calculations employing the TZP/TZ2P triple-zeta basis. From the recent experimental rovibrational interaction constants αC and αB, new accurate equilibrium rotational constants Ce and Be have been derived for the symmetric top molecule PF3, which were used to derive the equilibrium geometry of this molecule: re(F-P) = 1.560986 (43) Å; θe(FPF) = 97.566657 (64)°.
Accurate monotone cubic interpolation
NASA Technical Reports Server (NTRS)
Huynh, Hung T.
1991-01-01
Monotone piecewise cubic interpolants are simple and effective. They are generally third-order accurate, except near strict local extrema where accuracy degenerates to second-order due to the monotonicity constraint. Algorithms for piecewise cubic interpolants, which preserve monotonicity as well as uniform third and fourth-order accuracy are presented. The gain of accuracy is obtained by relaxing the monotonicity constraint in a geometric framework in which the median function plays a crucial role.
Accurate Finite Difference Algorithms
NASA Technical Reports Server (NTRS)
Goodrich, John W.
1996-01-01
Two families of finite difference algorithms for computational aeroacoustics are presented and compared. All of the algorithms are single step explicit methods, they have the same order of accuracy in both space and time, with examples up to eleventh order, and they have multidimensional extensions. One of the algorithm families has spectral like high resolution. Propagation with high order and high resolution algorithms can produce accurate results after O(10(exp 6)) periods of propagation with eight grid points per wavelength.
NASA Technical Reports Server (NTRS)
Fortenberry, Ryan C.; Crawford, T. Daniel; Lee, Timothy J.
2012-01-01
The A 1B1 <-1A0 excitation into the dipole-bound state of the cyanomethyl anion (CH2CN??) has been hypothesized as the carrier for one di use interstellar band. However, this particular molecular system has not been detected in the interstellar medium even though the related cyanomethyl radical and the isoelectronic ketenimine molecule have been found. In this study we are employing the use of proven quartic force elds and second-order vibrational perturbation theory to compute accurate spectroscopic constants and fundamental vibrational frequencies for X 1A0 CH2CN?? in order to assist in laboratory studies and astronomical observations. Keywords: Astrochemistry, ISM: molecular anions, Quartic force elds, Rotational constants, Vibrational frequencies
A novel single-molecule study to determine protein--protein association constants.
Ratcliff, G C; Erie, D A
2001-06-20
Atomic force microscopy (AFM) is traditionally used as an imaging technique to gain qualitative information for a biological system. We have successfully used the imaging capabilities of the AFM to determine protein-protein association constants. We have developed a method to measure the molecular weight of a protein based on its volume determined from AFM images. Our volume determination method allows for rapid, accurate analysis of large protein populations. On the basis of the measured volume, the fraction of monomers as dimers was determined for the DNA helicase UvrD, and the dissociation constant (K(d)) for the helicase was calculated. We determined a K(d) for UvrD of 1.4 microM, which is in good agreement with published K(d) data obtained from analytical ultracentrifugation (AUC) studies. Our method provides a rapid method for determining protein-protein association constants. PMID:11403593
Buryak, Ilya; Vigasin, Andrey A.
2015-12-21
The present paper aims at deriving classical expressions which permit calculation of the equilibrium constant for weakly interacting molecular pairs using a complete multidimensional potential energy surface. The latter is often available nowadays as a result of the more and more sophisticated and accurate ab initio calculations. The water dimer formation is considered as an example. It is shown that even in case of a rather strongly bound dimer the suggested expression permits obtaining quite reliable estimate for the equilibrium constant. The reliability of our obtained water dimer equilibrium constant is briefly discussed by comparison with the available data based on experimental observations, quantum calculations, and the use of RRHO approximation, provided the latter is restricted to formation of true bound states only.
NASA Astrophysics Data System (ADS)
Buryak, Ilya; Vigasin, Andrey A.
2015-12-01
The present paper aims at deriving classical expressions which permit calculation of the equilibrium constant for weakly interacting molecular pairs using a complete multidimensional potential energy surface. The latter is often available nowadays as a result of the more and more sophisticated and accurate ab initio calculations. The water dimer formation is considered as an example. It is shown that even in case of a rather strongly bound dimer the suggested expression permits obtaining quite reliable estimate for the equilibrium constant. The reliability of our obtained water dimer equilibrium constant is briefly discussed by comparison with the available data based on experimental observations, quantum calculations, and the use of RRHO approximation, provided the latter is restricted to formation of true bound states only.
Space Shuttle astrodynamical constants
NASA Technical Reports Server (NTRS)
Cockrell, B. F.; Williamson, B.
1978-01-01
Basic space shuttle astrodynamic constants are reported for use in mission planning and construction of ground and onboard software input loads. The data included here are provided to facilitate the use of consistent numerical values throughout the project.
Constant potential pulse polarography
Christie, J.H.; Jackson, L.L.; Osteryoung, R.A.
1976-01-01
The new technique of constant potential pulse polarography, In which all pulses are to be the same potential, is presented theoretically and evaluated experimentally. The response obtained is in the form of a faradaic current wave superimposed on a constant capacitative component. Results obtained with a computer-controlled system exhibit a capillary response current similar to that observed In normal pulse polarography. Calibration curves for Pb obtained using a modified commercial pulse polarographic instrument are in good accord with theoretical predictions.
Absolute radiometry and the solar constant
NASA Technical Reports Server (NTRS)
Willson, R. C.
1974-01-01
A series of active cavity radiometers (ACRs) are described which have been developed as standard detectors for the accurate measurement of irradiance in absolute units. It is noted that the ACR is an electrical substitution calorimeter, is designed for automatic remote operation in any environment, and can make irradiance measurements in the range from low-level IR fluxes up to 30 solar constants with small absolute uncertainty. The instrument operates in a differential mode by chopping the radiant flux to be measured at a slow rate, and irradiance is determined from two electrical power measurements together with the instrumental constant. Results are reported for measurements of the solar constant with two types of ACRs. The more accurate measurement yielded a value of 136.6 plus or minus 0.7 mW/sq cm (1.958 plus or minus 0.010 cal/sq cm per min).
Spatial and temporal variations of fundamental constants
NASA Astrophysics Data System (ADS)
Levshakov, S. A.; Agafonova, I. I.; Molaro, P.; Reimers, D.
2010-11-01
Spatial and temporal variations in the electron-to-proton mass ratio, μ, and in the fine-structure constant, α, are not present in the Standard Model of particle physics but they arise quite naturally in grant unification theories, multidimensional theories and in general when a coupling of light scalar fields to baryonic matter is considered. The light scalar fields are usually attributed to a negative pressure substance permeating the entire visible Universe and known as dark energy. This substance is thought to be responsible for a cosmic acceleration at low redshifts, z < 1. A strong dependence of μ and α on the ambient matter density is predicted by chameleon-like scalar field models. Calculations of atomic and molecular spectra show that different transitions have different sensitivities to changes in fundamental constants. Thus, measuring the relative line positions, Δ V, between such transitions one can probe the hypothetical variability of physical constants. In particular, interstellar molecular clouds can be used to test the matter density dependence of μ, since gas density in these clouds is ~15 orders of magnitude lower than that in terrestrial environment. We use the best quality radio spectra of the inversion transition of NH3 (J,K)=(1,1) and rotational transitions of other molecules to estimate the radial velocity offsets, Δ V ≡ Vrot - Vinv. The obtained value of Δ V shows a statistically significant positive shift of 23±4stat±3sys m s-1 (1σ). Being interpreted in terms of the electron-to-proton mass ratio variation, this gives Δμ/μ = (22±4stat±3sys)×10-9. A strong constraint on variation of the quantity F = α2/μ in the Milky Way is found from comparison of the fine-structure transition J=1-0 in atomic carbon C i with the low-J rotational lines in carbon monoxide 13CO arising in the interstellar molecular clouds: |Δ F/F| < 3×10-7. This yields |Δ α/α| < 1.5×10-7 at z = 0. Since extragalactic absorbers have gas densities