Molecular Modeling and Simulation. Applications and Perspectives
Structure, dynamics, and functioning of hydrated lipid bilayers - model cell membranes - are governed by a thin balance of intermolecular interactions between constituents of these systems. Besides the hydrophobic effect, which determines the overall bilayer skeleton, important contribution is made by Hbonds between lipids, water, and ions. This determines crucial phenomena in cell membranes: dynamic clustering, hydration, fine tuning of microscopic physico-chemical properties, which permit fast adaptation of membranes to external agents (e.g., proteins). Characteristics of H-bonds (strength, spatial location, etc.) dramatically depend on local polarity properties of water-lipid environment. Here, we calculated free energies of H-bonded complexes between lipids and water in explicit solvents of different polarity (water, methanol, chloroform) mimicking membrane environment at different depth. The strongest H-bonds were observed in nonpolar environment, although the overall bilayer organization imposes serious limitations on the distribution of various types of H-bonds over hydrophobic/hydrophilic regions (corresponding to dielectric media with low and high permeability). This creates a delicate balance, which determines a unique H-bonding pattern for each particular lipid bilayer. This was confirmed via atomistic molecular dynamics (MD) of several hydrated lipid bilayers. Understanding of the factors regulating H-bonding propensities in such systems is indispensable for rational design of new membranelike materials with predefined properties. One example - an artificial lipid with engineered hydroxyl group - is studied via MD simulations. It is shown that such lipids can induce significant changes of key characteristics of model membranes. This opens new avenues in goal-oriented design of artificial membranes with engineered properties.
Atomistic aspects of the structural organization, dynamics, and functioning of hydrated lipid bilayers - model cell membranes - are primarily governed by the fine balance of intermolecular interactions between all constituents of these systems. Besides the hydrophobic effect, which shapes the overall skeleton of lipid membranes, very important contribution to their behavior is made by hydrogen bonds (H-bonds) between lipid head groups. The latter determine such crucial phenomena in cell membranes, like dynamic ultra-nanodomain organization, hydration, fine-tuning of microscopic physico-chemical properties that allow the membrane to adapt quickly when binding/insertion external agents (proteins, etc.) The characteristics of such H-bonds (strength, spatial localization, etc.) dramatically depend on the local polarity properties of the lipid-water environment. In this work, we calculated free energies of H-bonded complexes between typical donor (NH3+, NH, OH) and acceptor (C=O, OH, COO-, COOH) groups of lipids in vacuo and in a set of explicit solvents with dielectric constants (ε) from 1 to 78.3, which mimic membrane environment at different depth. This was done using Monte Carlo simulations and an assessment of the corresponding Potential of Mean Force profiles. The strongest H-bonded complexes were observed in the nonpolar environment and their strength increased sharply with decreasing ε below 17. When ε changed, the largest free energy gain (> 10.8 kcal/mol) was observed for pairs of acceptors C=O and O(H) with donor NH3+. The complexation of the same acceptors with NH-donor in this range of ε was rather less sensitive to the environmental polarity: by ~1.5 kcal/mol. Dielectric-dependent interactions of polar lipid groups with water were evaluated as well. The results explain the delicate balance that determines the unique pattern of H-bonds for a particular lipid bilayer. Understanding the factors that regulate the propensity to H-bonding in lipid bilayers provides a fundamental basis for the rational design of new membrane nano-objects with predefined properties.
How is a water-soluble globular protein able to spontaneously cross a cellular membrane? It is commonly accepted that it undergoes significant structural rearrangements on the lipid-water interface, thus acquiring membrane binding and penetration ability. In this study molecular dynamics (MD) simulations have been used to explore large-scale conformational changes of the globular viscumin A chain in a complex environment – comprising urea and chloroform/methanol (CHCl3/MeOH) mixture. Being well-packed in aqueous solution, viscumin A undergoes global structural rearrangements in both organic media. In urea, the protein is “swelling” and gradually loses its long-distance contacts, thus resembling the “molten globule” state. In CHCl3/MeOH, viscumin A is in effect turned “inside out”. This is accompanied with strengthening of the secondary structure and surface exposure of hydrophobic epitopes originally buried inside the globule. Resulting solvent-adapted models were further subjected to Monte Carlo simulations with an implicit hydrophobic slab membrane. In contrast to only a few point surface contacts in water and two short regions with weak protein-lipid interactions in urea, MD-derived structures in CHCl3/MeOH reveal multiple determinants of membrane interaction. Consequently it is now possible to propose a specific pathway for the structural adaptation of viscumin A with respect to the cell membrane – a probable first step of its translocation into cytoplasmic targets.
A model for organizing cargo transportation between two node stations connected by a railway line which contains a certain number of intermediate stations is considered. The movement of cargo is in one direction. Such a situation may occur, for example, if one of the node stations is located in a region which produce raw material for manufacturing industry located in another region, and there is another node station. The organization of freight traﬃc is performed by means of a number of technologies. These technologies determine the rules for taking on cargo at the initial node station, the rules of interaction between neighboring stations, as well as the rule of distribution of cargo to the ﬁnal node stations. The process of cargo transportation is followed by the set rule of control. For such a model, one must determine possible modes of cargo transportation and describe their properties. This model is described by a ﬁnite-dimensional system of diﬀerential equations with nonlocal linear restrictions. The class of the solution satisfying nonlocal linear restrictions is extremely narrow. It results in the need for the “correct” extension of solutions of a system of diﬀerential equations to a class of quasi-solutions having the distinctive feature of gaps in a countable number of points. It was possible numerically using the Runge–Kutta method of the fourth order to build these quasi-solutions and determine their rate of growth. Let us note that in the technical plan the main complexity consisted in obtaining quasi-solutions satisfying the nonlocal linear restrictions. Furthermore, we investigated the dependence of quasi-solutions and, in particular, sizes of gaps (jumps) of solutions on a number of parameters of the model characterizing a rule of control, technologies for transportation of cargo and intensity of giving of cargo on a node station.
Event logs collected by modern information and technical systems usually contain enough data for automated process models discovery. A variety of algorithms was developed for process models discovery, conformance checking, log to model alignment, comparison of process models, etc., nevertheless a quick analysis of ad-hoc selected parts of a journal still have not get a full-fledged implementation. This paper describes an ROLAP-based method of multidimensional event logs storage for process mining. The result of the analysis of the journal is visualized as directed graph representing the union of all possible event sequences, ranked by their occurrence probability. Our implementation allows the analyst to discover process models for sublogs defined by ad-hoc selection of criteria and value of occurrence probability
The geographic information system (GIS) is based on the first and only Russian Imperial Census of 1897 and the First All-Union Census of the Soviet Union of 1926. The GIS features vector data (shapefiles) of allprovinces of the two states. For the 1897 census, there is information about linguistic, religious, and social estate groups. The part based on the 1926 census features nationality. Both shapefiles include information on gender, rural and urban population. The GIS allows for producing any necessary maps for individual studies of the period which require the administrative boundaries and demographic information.
Existing approaches suggest that IT strategy should be a reflection of business strategy. However, actually organisations do not often follow business strategy even if it is formally declared. In these conditions, IT strategy can be viewed not as a plan, but as an organisational shared view on the role of information systems. This approach generally reflects only a top-down perspective of IT strategy. So, it can be supplemented by a strategic behaviour pattern (i.e., more or less standard response to a changes that is formed as result of previous experience) to implement bottom-up approach. Two components that can help to establish effective reaction regarding new initiatives in IT are proposed here: model of IT-related decision making, and efficiency measurement metric to estimate maturity of business processes and appropriate IT. Usage of proposed tools is demonstrated in practical cases.
This volume presents new results in the study and optimization of information transmission models in telecommunication networks using different approaches, mainly based on theiries of queueing systems and queueing networks .
The paper provides a number of proposed draft operational guidelines for technology measurement and includes a number of tentative technology definitions to be used for statistical purposes, principles for identification and classification of potentially growing technology areas, suggestions on the survey strategies and indicators. These are the key components of an internationally harmonized framework for collecting and interpreting technology data that would need to be further developed through a broader consultation process. A summary of definitions of technology already available in OECD manuals and the stocktaking results are provided in the Annex section.