The effect of horizontal resolution on simulation of very extreme US precipitation events in a global atmosphere model

We investigate the ability of a global atmospheric general circulation model (AGCM) to reproduce observed 20 year return values of the annual maximum daily precipitation totals over the continental United States as a function of horizontal resolution. We find that at the high resolutions enabled by contemporary supercomputers, the AGCM can produce values of comparable magnitude to high quality observations. However, at the resolutions typical of the coupled general circulation models used in the Fourth Assessment Report of the Intergovernmental Panel on Climate Change, the precipitation return values are severely underestimated.

An adaptive drug delivery design using neural networks for effective treatment of infectious diseases: A simulation study

An adaptive drug delivery design is presented in this paper using neural networks for effective treatment of infectious diseases. The generic mathematical model used describes the coupled evolution of concentration of pathogens, plasma cells, antibodies and a numerical value that indicates the relative characteristic of a damaged organ due to the disease under the influence of external drugs. From a system theoretic point of view, the external drugs can be interpreted as control inputs, which can be designed based on control theoretic concepts. In this study, assuming a set of nominal parameters in the mathematical model, first a nonlinear controller (drug administration) is designed based on the principle of dynamic inversion. This nominal drug administration plan was found to be effective in curing "nominal model patients" (patients whose immunological dynamics conform to the mathematical model used for the control design exactly. However, it was found to be ineffective in curing "realistic model patients" (patients whose immunological dynamics may have off-nominal parameter values and possibly unwanted inputs) in general. Hence, to make the drug delivery dosage design more effective for realistic model patients, a model-following adaptive control design is carried out next by taking the help of neural networks, that are trained online. Simulation studies indicate that the adaptive controller proposed in this paper holds promise in killing the invading pathogens and healing the damaged organ even in the presence of parameter uncertainties and continued pathogen attack. Note that the computational requirements for computing the control are very minimal and all associated computations (including the training of neural networks) can be carried out online. However it assumes that the required diagnosis process can be carried out at a sufficient faster rate so that all the states are available for control computation.

An Insight to the Dynamics of Conserved Water Molecular Triad in IMPDH II (Human): Recognition of Cofactor and Substrate to Catalytic Arg 322

Inosine 5' monophosphate dehydrogenase (IMPDH II) is a key enzyme involved in the de novo biosynthesis pathway of purine nucleotides and is also considered to be an excellent target for cancer inhibitor design. The conserve R 322 residue (in human) is thought to play some role in the recognition of inhibitor and cofactor through the catalytic D 364 and N 303. The 15 ns simulation and the water dynamics of the three different PDB structures (1B3O, 1NF7, and 1NFB) of human IMPDH by CHARMM force field have clearly indicated the involvement of three conserved water molecules (W-L, W-M, and W-C) in the recognition of catalytic residues (R 322, D 364, and N 303) to inhibitor and cofactor. Both the guanidine nitrogen atoms (NH1 and NH 2) of the R 322 have anchored the di- and mono-nucleotide (cofactor and inhibitor) binding domains via the conserved W-C and W-L water molecules. Another conserved water molecule W-M seems to bridge the two domains including the R 322 and also the W-C and W-L through seven centers H-bonding coordination. The conserved water molecular triad (W-C - W-M - W-L) in the protein complex may thought to play some important role in the recognition of inhibitor and cofactor to the protein through R 322 residue.

Insight into the early stages of thermal unfolding of peanut agglutinin by molecular dynamics simulations

Peanut agglutinin is a homotetrameric nonglycosylated protein. The protein has a unique open quaternary structure. Molecular dynamics simulations have been employed follow the atomistic details of its unfolding at different temperatures. The early events of the deoligomerization of the protein have been elucidated in the present study. Simulation trajectories of the monomer as well as those of the tetramer have been compared and the tetramer is found to be substantially more stable than its monomeric counterpart. The tetramer shows retention of most of its.. secondary structure but considerable loss of the tertiary structure at high temperature. e generation of a This observation impies the molten globule-like intermediate in the later stages of deoligomerization. The quaternary structure of the protein has weakened to a large extent, but none of the subunits are separated. In addition, the importance of the metal-binding to the stability of the protein structure has also been investigated. Binding of the metal ions not only enhances the local stability of the metal-ion binding loop, but also imparts a global stability to the overall structure. The dynamics of different interfaces vary significantly as probed through interface clusters. The differences are substantially enhanced at higher temperatures. The dynamics and the stability of the interfaces have been captured mainly by cluster analysis, which has provided detailed information on the thermal deoligomerization of the protein.

Necessity for quantum mechanical simulation for the future technology nodes

In this paper we present and compare the results obtained from semi-classical and quantum mechanical simulation for a Double Gate MOSFET structure to analyze the electrostatics and carrier dynamics of this device. The geometries like gate length, body, thickness of this device have been chosen according to the ITRS specification for the different technology nodes. We have shown the extent of deviation between the semi-classical and quantum mechanical results and hence the need of quantum simulations for the promising nanoscale devices in the future technology nodes predicted in ITRS.

Solution of MDPS using simulation-based value iteration

This article proposes a three-timescale simulation based algorithm for solution of infinite horizon Markov Decision Processes (MDPs). We assume a finite state space and discounted cost criterion and adopt the value iteration approach. An approximation of the Dynamic Programming operator T is applied to the value function iterates. This 'approximate' operator is implemented using three timescales, the slowest of which updates the value function iterates. On the middle timescale we perform a gradient search over the feasible action set of each state using Simultaneous Perturbation Stochastic Approximation (SPSA) gradient estimates, thus finding the minimizing action in T. On the fastest timescale, the 'critic' estimates, over which the gradient search is performed, are obtained. A sketch of convergence explaining the dynamics of the algorithm using associated ODEs is also presented. Numerical experiments on rate based flow control on a bottleneck node using a continuous-time queueing model are performed using the proposed algorithm. The results obtained are verified against classical value iteration where the feasible set is suitably discretized. Over such a discretized setting, a variant of the algorithm of [12] is compared and the proposed algorithm is found to converge faster.

Two-Phase Thermodynamic Model for Efficient and Accurate Absolute Entropy of Water from Molecular Dynamics Simulations

Presented here is the two-phase thermodynamic (2PT) model for the calculation of energy and entropy of molecular fluids from the trajectory of molecular dynamics (MD) simulations. In this method, the density of state (DoS) functions (including the normal modes of translation, rotation, and intramolecular vibration motions) are determined from the Fourier transform of the corresponding velocity autocorrelation functions. A fluidicity parameter (f), extracted from the thermodynamic state of the system derived from the same MD, is used to partition the translation and rotation modes into a diffusive, gas-like component (with 3Nf degrees of freedom) and a nondiffusive, solid-like component. The thermodynamic properties, including the absolute value of entropy, are then obtained by applying quantum statistics to the solid component and applying hard sphere/rigid rotor thermodynamics to the gas component. The 2PT method produces exact thermodynamic properties of the system in two limiting states: the nondiffusive solid state (where the fluidicity is zero) and the ideal gas state (where the fluidicity becomes unity). We examine the 2PT entropy for various water models (F3C, SPC, SPC/E, TIP3P, and TIP4P-Ew) at ambient conditions and find good agreement with literature results obtained based on other simulation techniques. We also validate the entropy of water in the liquid and vapor phases along the vapor-liquid equilibrium curve from the triple point to the critical point. We show that this method produces converged liquid phase entropy in tens of picoseconds, making it an efficient means for extracting thermodynamic properties from MD simulations.

Effect of coordinated ions on structure and flexibility of parallel G-quadruplexes: A molecular dynamics study

ingle tract guanine residues can associate to form stable parallel quadruplex structures in the presence of certain cations. Nanosecond scale molecular dynamics simulations have been performed on fully solvated fibre model of parallel d(G(7)) quadruplex structures with Na+ or K+ ions coordinated in the cavity formed by the O6 atoms of the guanine bases. The AMBER 4.1 force field and Particle Mesh Ewald technique for electrostatic interactions have been used in all simulations. There quadruplex structures are stable during the simulation, with the middle four base tetrads showing root mean square deviation values between 0.5 to 0.8 Angstrom from the initial structure as well the high resolution crystal structure. Even in the absence of any coordinated ion in the initial structure, the G-quadruplex structure remains intact throughout the simulation. During the 1.1 ns MD simulation, one Nai counter ion from the solvent as well as several water molecules enter the central cavity to occupy the empty coordination sites within the parallel quadruplex and help stabilize the structure. Hydrogen bonding pattern depends on the nature of the coordinated ion, with the G-tetrad undergoing local structural variation to accommodate cations of different sizes. in the absence of any coordinated ion. due to strong mutual repulsion, O6 atoms within G-tetrad are forced farther apart from each other, which leads to a considerably different hydrogen bonding scheme within the G-tetrads and very favourable interaction energy between the guanine bases constituting a G-tetrad. However, a coordinated ion between G-tetrads provides extra stacking energy for the G-tetrads and makes the quadruplex structure more rigid. Na+ ions, within the quadruplex cavity, are more mobile than coordinated K+ ions. A number of hydrogen bonded water molecules are observed within the grooves of all quadruplex structures.

Sliding Modes for the Simulation of Mechanical and Electrical Systems Defined by Differential-Algebraic Equations

We offer a technique, motivated by feedback control and specifically sliding mode control, for the simulation of differential-algebraic equations (DAEs) that describe common engineering systems such as constrained multibody mechanical structures and electric networks. Our algorithm exploits the basic results from sliding mode control theory to establish a simulation environment that then requires only the most primitive of numerical solvers. We circumvent the most important requisite for the conventionalsimulation of DAEs: the calculation of a set of consistent initial conditions. Our algorithm, which relies on the enforcement and occurrence of sliding mode, will ensure that the algebraic equation is satisfied by the dynamic system even for inconsistent initial conditions and for all time thereafter. [DOI:10.1115/1.4001904]

Study Of The Hvdc-Torsional Interactions Through Digital Dynamic Simulation

This paper presents the detailed dynamic digital simulation for the study of phenomenon of torsional interaction between HVDC-Turbine generator shaft, dynamics using the novel converter model presented in [ 1 ] The system model includes detailed representation of the synchronous generator and the shaft dynamics, the ac and dc network transients. The results of a case study indicate the various factors that influence the torsional interaction.

Relaxation dominated by inertia: Solvation dynamics of a small ion in a dipolar solvent

It is shown from an analytical theory that the solvation dynamics of a small ion can be controlled largely by the inertial response of the dipolar solvent when the liquid is in the underdamped limit. It is also shown that this inertial response arises primarily from the long wavelength (with wavevector k≃0) processes which have a collective excitation-like behaviour. The long time decay is dominated by the processes occurring at molecular lengthscales. The theoretical results are in good agreement with recent computer simulation results.

A nanosecond molecular dynamics study of antiparallel d(G)(7) quadruplex structures: Effect of the coordinated cations

Nanosecond scale molecular dynamics simulations have been performed on antiparallel Greek key type d(G(7)) quadruplex structures with different coordinated ions, namely Na+ and K+ ion, water and Na+ counter ions, using the AMBER force field and Particle Mesh Ewald technique for electrostatic interactions. Antiparallel structures are stable during the simulation, with root mean square deviation values of similar to1.5 Angstrom from the initial structures. Hydrogen bonding patterns within the G-tetrads depend on the nature of the coordinated ion, with the G-tetrad undergoing local structural variation to accommodate different cations. However, alternating syn-anti arrangement of bases along a chain as well as in a quartet is maintained through out the MD simulation. Coordinated Na+ ions, within the quadruplex cavity are quite mobile within the central channel and can even enter or exit from the quadruplex core, whereas coordinated K+ ions are quite immobile. MD studies at 400 K indicate that K+ ion cannot come out from the quadruplex core without breaking the terminal G-tetrads. Smaller grooves in antiparallel structures are better binding sites for hydrated counter ions, while a string of hydrogen bonded water molecules are observed within both the small and large grooves. The hydration free energy for the K+ ion coordinated structure is more favourable than that for the Na+ ion coordinated antiparallel quadruplex structure.

Effect of coordinated ions on structure and flexiblity of parallel G-quandruplexes: a molecular dynamics study

Single tract guanine residues can associate to form stable parallel quadruplex structures in the presence of certain cations. Nanosecond scale molecular dynamics simulations have been performed on fully solvated fibre model of parallel d(G7) quadruplex structures with Na+ or K+ ions coordinated in the cavity formed by the 06 atoms of the guanine bases. The AMBER 4.1 force field and Particle Mesh Ewald technique for electrostatic interactions have been used in all simulations. These quadruplex structures are stable during the simulation, with the middle four base tetrads showing root mean square deviation values between 0.5 to 0.8 A from the initial structure as well the high resolution crystal structure. Even in the absence of any coordinated ion in the initial structure, the G-quadruplex structure remains intact throughout the simulation. During the 1.1 ns MD simulation, one Na+ counter ion from the solvent as well as several water molecules enter the central cavity to occupy the empty coordination sites within the parallel quadruplex and help stabilize the structure. Hydrogen bonding pattern depends on the nature of the coordinated ion, with the G-tetrad undergoing local structural variation to accommodate cations of different sizes. In the absence of any coordinated ion, due to strong mutual repulsion, 06 atoms within G-tetrad are forced farther apart from each other, which leads to a considerably different hydrogen bonding scheme within the G-tetrads and very favourable interaction energy between the guanine bases constituting a G-tetrad. However, a coordinated ion between G-tetrads provides extra stacking energy for the G-tetrads and makes the quadruplex structure more rigid. Na+ ions, within the quadruplex cavity, are more mobile than coordinated K+ ions. A number of hydrogen bonded water molecules are observed within the grooves of all quadruplex structures

Molecular dynamics simulations on parallel and antiparallel C.G*G triplexes

Molecular dynamics (MD) studies have been carried out on the Hoogsteen hydrogen bonded parallel and the reverse Hoogsteen hydrogen banded antiparallel C.G*G triplexes. Earlier, the molecular mechanics studies had shown that the parallel structure was energetically more favourable than the antiparallel structure. To characterize the structural stability of the two triplexes and to investigate whether the antiparallel structure can transit to an energetically more favourable structure, due to the local fluctuations in the structure during the MD simulation, the two structures were subjected to 200ps of constant temperature vacuum MD simulations at 300K. Initially no constraints were applied to the structures and it was observed that for the antiparallel tripler, the structure showed a large root mean square deviation from the starting structure within the first 12ps and the N4-H41-O6 hydrogen bond in the WC duplex got distorted due to a high propeller twist and a moderate increase in the opening angle in the basepairs. Starting from an initial value of 30 degrees, helical twist of the average structure from this simulation had a value of 36 degrees, while the parallel structure stabilized at a twist of 33 degrees. In spite of the hydrogen bond distortions in the antiparallel tripler, it was energetically comparable to the parallel tripler. To examine the structural characteristics of an undistorted structure, another MD simulation was performed on the antiparallel tripler by constraining all the hydrogen bonds. This structure stabilized at an average twist of 33 degrees. In the course of the dynamics though the energy of the molecule - compared to the initial structure - improved, it did not become comparable to the parallel structure. Energy minimization studies performed in the presence of explicit water and counterions also showed the two structures to be equally favourable energetically Together these results indicate that the parallel C.G*G tripler with Hoogsteen hydrogen bonds also represents a stereochemically and energetically favourable structure for this class of triplexes.

Sequence Independent Recombination Triple Helices: A Molecular Dynamics Study

Recent experimental studies have shown that the Rec-A mediated homologous recombination reaction involves a triple helical intermediate, in which the third strand base forms hydrogen bonds with both the bases in the major groove of the Watson-Crick duplex. Such 'mixed' hydrogen bonds allow formation of sequence independent triplexes. DNA triple helices involving 'mixed' hydrogen bonds have been studied, using model building, molecular mechanics (MM) and molecular dynamics (MD). Models were built for a tripler comprising all four possible triplets viz., G.C*C, C.G*G, A.T*T and T.A*A. To check the stability of all the 'mixed' hydrogen bonds in such triplexes and the conformational preferences of such tripler structures, MD studies were carried out starting from two structures with 30 degrees and 36 degrees twist between the basepairs. It was observed that though the two triplexes converged towards a similar structure, the various hydrogen bonds between the WC duplex and the third strand showed differential stabilities. An MD simulation with restrained hydrogen bonds showed that the resulting structure was stable and remained close to the starting structure. These studies help us in defining stable hydrogen bond geometries involving the third strand and the WC duplex. It was observed that in the C.G*G triplets the N7 atom of the second strand is always involved in hydrogen bonding. In the G.C*C triplets, either N3 or O2 in the third strand cytosine can interchangeably act as a hydrogen bond acceptor.