Molecular systems with open boundaries: Theory and simulation

Molecular simulation is a mature and versatile tool set widely utilized in many subjects with more than 30,000 publications each year. However, its methodology development has been struggling with a tradeoff between accuracy/resolution and speed, significant improvement of both beyond present state of the art is necessary to reliably substitute many expensive and laborious experiments in molecular biology, materials science and nanotechnology. Previously, the ubiquitous issue regarding severe wasting of computational resources in all forms of molecular simulations due to repetitive local sampling was raised, and the local free energy landscape approach was proposed to address it. This approach is derived from a simple idea of first learning local distributions, and followed by dynamic assembly of which to infer global joint distribution of a target molecular system. When compared with conventional explicit solvent molecular dynamics simulations, a simple and approximate implementation of this theory in protein structural refinement harvested acceleration of about six orders of magnitude without loss of accuracy. While this initial test revealed tremendous benefits for addressing repetitive local sampling, there are some implicit assumptions need to be articulated. Here, I present a more thorough discussion of repetitive local sampling; potential options for learning local distributions; a more general formulation with potential extension to simulation of near equilibrium molecular systems; the prospect of developing computation driven molecular science; the connection to mainstream residue pair distance distribution based protein structure prediction/refinement; and the fundamental difference of utilizing averaging from conventional molecular simulation framework based on potential of mean force. This more general development is termed the local distribution theory to release the limitation of strict thermodynamic equilibrium in its potential wide application in general soft condensed molecular systems.

SCELib3.0: The new revision of SCELib, the parallel computational library of molecular properties in the Single Center Approach

In this work, we address two critical aspects of calculation of the free energy differences in molecular systems from molecular simulations. The first aspect involves checking whether the calculated free energy difference depends significantly on the extent of perturbation used for accomplishment of a given transformation. The second aspect of interest is to verify if the sampling errors in calculating the free energy differences between the wild-type molecule and a mutated one in its free state and in a complex are similar, or not, for a finite-length dynamic simulation. The reliability of the free energy estimates obtained from molecular simulations using thermodynamic cycles depends in part on this fact. For investigating these aspects, we use a self-transformation scheme in which a transformation of a part of a molecular system into itself is considered. We perform MD simulations of DNA fragments in which a part of a specific base is subjected to such a self-transformation. Results indicate that the estimated free energy differences do not depend significantly on the extent of perturbation used to achieve the transformation. Interestingly, the variation in the cumulative free energy difference, ΔA, with the coupling parameter, λ, depends significantly on the extent of perturbation. We examine the physical basis of the observed nature of the variation of the accumulated free energy difference, ΔA, against the λ value in the case of a self-transformation. In a thermodynamic cycle, the sampling errors due to the finite-length simulation for the molecular system are found to be similar to each other for the two perturbations (free and in a complex) justifying the use of such approach in calculating ΔΔA in molecular complexes. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 877-885, 1999.

Van der Waals (vdW) interactions are ubiquitous in molecules and condensed matter, and play a crucial role in determining the structure, stability, and function for a wide variety of systems. The accurate prediction of these interactions from first principles is a substantial challenge because they are inherently quantum mechanical phenomena that arise from correlations between many electrons within a given molecular system. We introduce an efficient method that accurately describes the nonadditive many-body vdW energy contributions arising from interactions that cannot be modeled by an effective pairwise approach, and demonstrate that such contributions can significantly exceed the energy of thermal fluctuations--a critical accuracy threshold highly coveted during molecular simulations--in the prediction of several relevant properties. Cases studied include the binding affinity of ellipticine, a DNA-intercalating anticancer agent, the relative energetics between the A- and B-conformations of DNA, and the thermodynamic stability among competing paracetamol molecular crystal polymorphs. Our findings suggest that inclusion of the many-body vdW energy is essential for achieving chemical accuracy and therefore must be accounted for in molecular simulations.

During recent decades it has become feasible to simulate the dynamics of molecular systems on a computer. The method of molecular dynamics (MD) solves Newton's equations of motion for a molecular system, which results in trajectories for all atoms in the system. From these atomic trajectories a variety of properties can be calculated. The aim of computer simulations of molecular systems is to compute macroscopic behavior from microscopic interactions. The main contributions a microscopic consideration can offer are (1) the understanding and (2) interpretation of experimental results, (3) semiquantitative estimates of experimental results, and (4) the capability to interpolate or extrapolate experimental data into regions that are only difficultly accessible in the laboratory. One of the two basic problems in the field of molecular modeling and simulation is how to efficiently search the vast configuration space which is spanned by all possible molecular conformations for the global low (free) energy regions which will be populated by a molecular system in thermal equilibrium. The other basic problem is the derivation of a sufficiently accurate interaction energy function or force field for the molecular system of interest. An important part of the art of computer simulation is to choose the unavoidable assumptions, approximations and simplifications of the molecular model and computational procedure such that their contributions to the overall inaccuracy are of comparable size, without affecting significantly the property of interest. Methodology and some practical applications of computer simulation in the field of (bio)chemistry will be reviewed.

Analysis of a two dimensional molecular Berry phase system

The properties of water at physiological conditions can be modelled at different levels of resolution: (1) sub-atomic models that take into account electronic degrees of freedom, (2) atomic models that only account for atomic degrees of freedom and (3) supra-molecular models that only involve some supra-molecular degrees of freedom. To enhance the computational efficiency of molecular simulation, models at different levels of resolution should be simultaneously usable for different parts of a system for which the level of detail of interest is different. This requires these different types of models to be compatible with each other. In the present study, the compatibility of two polarisable models for liquid water, COS/G2 and COS/D, with a non-polarisable model for liquid water, SPC, is investigated. It is shown that these models are compatible. The polarisable models can thus be used to solvate biomolecules described by a biomolecular force field that is compatible with the SPC water model.

The problem of simulating light scattering patterns of polymerization induced phase separation processes by the mechanism of nucleation and growth is addressed with the objective of reducing the number of computations required to carry out the simulation. A method, based on the Fast Fourier Transform (FFT), that takes advantage of the spherical nature of the phase separated domains, is proposed. Contrary to the case in which the spherical particles are randomly placed in arbitrary locations in the scattering volume, the proposed computational scheme requires the locations not to be arbitrary but to belong to a previously defined equally spaced grid. This last constraint determines levels of resolution in which the simulation can be performed. The FFT based method is tested with a morphology previously generated with a model of the phase separation process. The light scattering pattern corresponding to this morphology, mainly represented through the particle size distribution of the spherical separated domains, has been simulated at different levels of resolution of the grid placed in the scattering domain and of the sizes of the domains. It has been found that the original morphology represented by a distribution with 17 different sizes can be approximated by a smaller number, while keeping the total volume of particles the same, without a noticeable loss of precision. This, together with the fact that the computations can be performed at different levels of resolution, gives the chance to explore an important number of approximations to the problem, many of which produce, using the proposed method, results that are comparable to those obtained at higher levels of resolution, with the advantage of requiring a smaller number of computations.

Most human diseases are complex multi-factorial diseases resulting from the combination of various genetic and environmental factors. In the KEGG database resource (http://www.genome.jp/kegg/), diseases are viewed as perturbed states of the molecular system, and drugs as perturbants to the molecular system. Disease information is computerized in two forms: pathway maps and gene/molecule lists. The KEGG PATHWAY database contains pathway maps for the molecular systems in both normal and perturbed states. In the KEGG DISEASE database, each disease is represented by a list of known disease genes, any known environmental factors at the molecular level, diagnostic markers and therapeutic drugs, which may reflect the underlying molecular system. The KEGG DRUG database contains chemical structures and/or chemical components of all drugs in Japan, including crude drugs and TCM (Traditional Chinese Medicine) formulas, and drugs in the USA and Europe. This database also captures knowledge about two types of molecular networks: the interaction network with target molecules, metabolizing enzymes, other drugs, etc. and the chemical structure transformation network in the history of drug development. The new disease/drug information resource named KEGG MEDICUS can be used as a reference knowledge base for computational analysis of molecular networks, especially, by integrating large-scale experimental datasets.

The minor expressiveness of text with respect to visual features doesn't allow to fully exploit capabilities of human memory. For this reason retrieval based on visual contents has been identified as the means to provide an effective retrieval. The relative relevance of visual elements depends on user's subjectivity (which is not known in advance) and on the context of application. To cope with this problem, the description of image visual contents should exploit different levels of detail in image representation. In the following we present the PICASSO system, which supports image indexing and retrieval based on shapes, colors, and spatial relationships. The system exploits a pyramidal representation of the images which are analyzed at different levels of resolution. Multiple descriptions of image properties are created at different levels of resolution thus allowing effective retrieval through specific queries as well as imprecise ones. Retrieval results for a sample database of pictorial images are reported, with efficiency and effectiveness measures.

The goal of this paper is to present a quantitative study about Telco churn analysis and the inherent problems of its application and computer processing. An independent customer characterizes the approach and the pre-processing step uses the wavelet transform concept; the pattern classification problem is solved by an artificial neural network (RBFRadial Basis Function). The signal representation considers different levels of resolution (multi-resolution). This idea is frequently used in image/video processing where general image versions with a low resolution are stored in different levels of resolution. The concepts of multi-resolution have been implemented by a digital filter bank, Hi-pass and Low-pass. Each sub-band will give the best resolution, for each spectral region. The idea is to look for a spectral transient. A scalable Daubechies’ function db 2 and db 3 were tested for this study and the results were used as input for the RBF neural network. Daubechies’ function has shown important properties as for instance, orthogonality and scalability, which are not presented by Morlet’s function. Some results of the experiment were presented to point out the performance of the wavelet pre-processing approach.

Avian communities living in a complex environment were studied by censuses of singing males, using several levels of resolution which focussed on different properties of the community. Within each level of resolution, various community parameters in two grassland habitat types were calculated over the entire breeding season, and for census intervals within the breeding season. The community level of resolution focussed on community—wide patterns, such as total density and total biomass, in order to reveal constraints operating on all species in each habitat. An intermediate level of resolution focussed on relative properties of species such as relative abundances, species richness, and dominance concentration. At the individual species level of resolution, densities and identities of species were the properties upon which the analysis focussed. These techniques allowed characterization of responses of the avian communities to complex changes in the system in which they were embedded. Long—term averages in monthly rainfall on the sites used for this study indicated a bimodal distribution of rainfall. The first peak occurred in December and the second in July and August. During the two years of study, summer rainfall was similar, but winter rainfall in 1983 was °2—3 times as great as in 1982. Avian communities in habitats with mesquite trees (mesquite savannah) responded differently than communities in grassland habitats, and these responses could be seen at different levels of resolution. Peak densities and biomass occurred during May—June in mesquite savannah habitats, while grassland communities achieved highest densities and biomass during July and August. Average density per individual showed little seasonal pattern, but was lower for mesquite savannah communities than for grassland communities. Species richness increased in mesquite savannah habitats in 1983, but decreased in grassland habitats that year. Patterns of evenness and dominance concentration suggested that in 1983, rare species of large body size were added to the community in mesquite savannah, while in grassland habitats, species already present during 1982 increased in density. A community ordination revealed that mesquite savannah habitats were dominated numerically by small—bodied insectivorous species during the early part of the breeding season but became similar to grassland communities in July and August. Grassland communities were dominated by large—bodied emberizine finches. These characteristics of the avian communities corresponded closely to the phenology of important primary producers. Mesquite produces leaves high in nutritional value and produces flowers during April—June; thereafter older leaves decline in nutrient content and flowers disappear. These changes in mesquite productivity undoubtedly produce corresponding changes in insect communities exploitable by small—bodied insectivores. Perennial grasses concentrate aboveground productivity to July—August and insect communities associated with grasses increased in biomass during this period, thus increasing resources available for breeding. These results suggest that avian community responses to complex changes in their environments can be identified and related to outside inputs into the environment, such as rainfall. Identification of community responses is facilitated by emphasis on several observational scales. Communities appear individualistic to observers because (1) adaptational units of species are probably much larger than study areas; (2) species ability to adapt to local conditions might be diluted by gene flow among populations; and (3) if most evolutionary change occurs during speciation, then species adaptations will reflect a relatively narrow range of selection pressures that operated briefly on the species during the past.

A new mechanism for realizing negative permeability with a three-level ladder-type atomic (or molecular) system at microwave frequency is suggested. The explicit expressions for the magnetic permeability of both steady and transient cases are presented. Compared with the previous schemes to realize negative permeability within the framework of classical electromagnetic theory, the most remarkable feature in the present mechanism is that it can realize the isotropic material with negative permeability. Such a permeability can be controllably manipulated by external coupling fields and could lead to potential applications in quantum optical devices.

This paper presents an O(N) algorithm and its preliminary computer simulation results for virtual prototyping of molecular systems with a simple chain structure. The algorithm is based on proper integration between an internal coordinate method (ICM) and a multibody molecular model. ICM method makes the use of recursive relations possible between two adjacent subsets within a molecular system. The multibody molecular model takes the benefits of freezing degrees of freedom of some lightly excited high frequency bonds. Because these high frequency bonds would force the use of very small integration step sizes, which severely limits the time scales for virtual prototyping of dynamics of molecular conformation over long periods of time. Thus a new multiscale model and efficient algorithm is produced to increase computational efficiency for virtual prototyping of dynamical behaviors of molecular confirmation. This paper will be initially directed towards introduction of the new model and algorithm. Then attention will be turned to the implementation of the algorithm at macro scale, which can be used to demonstrate the validity of the procedure and algorithm. Final focus will be turned to the implementation of the algorithm to a simple molecular chain at micro scale. The algorithm gives an O(N) computational performance for formation/solution of equations of motion for a molecular chain system.

Continuous advancements in DNA nanotechnology have resulted in innovative information security strategies utilizing biomolecular-based encryption mechanisms to achieve effective protection and reliable storage. However, existing molecular encryption schemes are limited in their practical expansion due to their focus on the precise design and strict management of the key itself while neglecting the impact of complex environments, causing them to suffer from insufficient concealment and poor adaptability to complex access control scenarios. Here, we propose a pH-regulated camouflage strategy that significantly enhances the encryption concealment of molecular systems. Using pH-regulated logical operation transformations, we establish a switchable cascaded logic operation strategy that implements a two-layer DNA molecular firewall access control system. By integrating two distinct camouflage rules, the system constructs four differentiated access modes. This design effectively prevents unauthorized access, conceals true input addresses, and deceives potential attackers, thereby ensuring internal information security. This approach provides a simple method for the design and management of molecular systems and is expected to be applied in fields such as information security and environmental monitoring.