Exploring DNA groove water dynamics through hydrogen bond lifetime and orientational relaxation

Dynamics of water molecules in the grooves of DNA are of great interest both for practical (functionality of DNA) and fundamental (as examples of confined systems) interest. Here the authors employ atomistic molecular dynamics simulations to understand varying water dynamics at the minor and the major grooves of a 38 base-pair long DNA duplex in water. In order to understand and quantify the diversity in the nature of hydrogen bond due to many hydrogen bond donors and acceptors present in the four bases, they have undertaken study of hydrogen bond lifetime (HBLT) correlation functions of all the specific hydrogen bonds between the base atoms and water molecules. They find that the HBLT correlation functions are in general multiexponential, with the average lifetime depending significantly on the specificity and may thus be biologically relevant. The average hydrogen bond lifetime is longer in the minor groove than that in the major groove by almost a factor of 2. Analysis further shows that water hydrogen bonds with phosphate oxygen have substantially shorter lifetimes than those with the groove atoms. They also compute two different orientational time correlation functions (OTCFs) of the water molecules present at the major and the minor grooves and attempt to correlate OTCF with HBLT correlation function. The OTCFs in the minor groove exhibit three time scales, with the time constant of the slowest component one to two orders of magnitude longer than what is observed for bulk water. A slow component is also present for the major groove water but with shorter time constant. Interestingly, correlation between reformations allowed HBLT correlation function [C(HB)(t)] and the OTCF markedly deviates from each other in the grooves, indicating enhanced rigidity of water molecules in the grooves.     

Molecular drug design, synthesis and structure elucidation of a new specific target peptide based metallo drug for cancer chemotherapy as topoisomerase I inhibitor

To evaluate the biological preference of metallopeptide drugs in cancer cells, a new dinuclear copper(II) complex [Cu(2)(glygly)(2)(ppz)(H(2)O)(4)]·2H(2)O (1) (glygly = glycyl glycine anion and ppz = piperazine), was designed and synthesized as topoisomerase I inhibitor. The structural elucidation of the complex was done by elemental analysis, spectroscopic methods and single crystal X-ray diffraction. The in vitro DNA binding studies of complex 1 with CT DNA were carried out by employing different optical methods viz. UV-vis, fluorescence and circular dichroism. The molecular docking technique was also utilized to ascertain the mechanism and mode of action towards the molecular target DNA and enzymes. Complex 1 cleaves pBR322 DNA via an oxidative mechanism and strongly binds to the DNA minor groove. Furthermore, complex 1 exhibits significant inhibitory effects on the catalytic activity of topoisomerase I at a very low concentration, ~12.5 μM, in addition to its excellent SOD mimics (IC(50)~0.086 μM).     

Analysis of membrane tank-tread of nonspherical capsules and red blood cells

We present an analysis of membrane motion of deformable capsules and red blood cells suspended in a linear shear flow and undergoing swinging and tumbling motions using three-dimensional numerical simulations. This study is motivated by the theory of the shape-preserving cells which predicts that the direction of the membrane rotation depends on the cell orientation and reverses at every 45° inclination angle of the cell major axis with respect to the external flow direction. By considering large deformation of capsules and red blood cells, here we investigate how the shape oscillation affects the time dependence and the direction reversal of the membrane rotation. We find that the membrane tank-tread is highly time-dependent in nature and synchronized with the time-dependent deformation. The maximum and minimum of the tank-tread velocity occur at and near the minimum and maximum deformation, respectively. For the swinging capsules and red blood cells, the direction of the membrane rotation is always along the direction of the external fluid rotation; however, a direction reversal occurs during the tumbling motion in which case the membrane rotates in the direction of the external fluid rotation when the major axis is mostly in the extensional quadrant of the shear flow, and in the opposite direction when it is mostly in the compressional quadrant. Unlike the theory which predicts the direction reversal at every 45° inclination angle irrespective of the control parameters, namely, the capillary number, viscosity ratio, and asphericity, we find that the angle at which the direction reversal occurs depends on these parameters. In particular, if the tumbling motion occurs by decreasing the capillary number, the membrane rotation is in the direction of the external flow rotation in the entire extensional quadrant, but in the opposite direction in the compressional quadrant, irrespective of the specific values of the capillary number. If the tumbling motion occurs by increasing the viscosity ratio and asphericity, the angle at which the direction reversal occurs depends on the specific values of these two parameters. The spatial variation of the tank-tread velocity also is analyzed and attributed to the straining motion of the external flow.      

Sensitivity of nucleation phenomena on range of interaction potential

Theoretical and computational investigations of nucleation have been plagued by the sensitivity of the phase diagram to the range of the interaction potential. As the surface tension depends strongly on the range of interaction potential and as the classical nucleation theory (CNT) predicts the free energy barrier to be directly proportional to the cube of the surface tension, one expects a strong sensitivity of nucleation barrier to the range of the potential; however, CNT leaves many aspects unexplored. We find for gas-liquid nucleation in Lennard-Jones system that on increasing the range of interaction the kinetic spinodal (KS) (where the mechanism of nucleation changes from activated to barrierless) shifts deeper into the metastable region. Therefore the system remains metastable for larger value of supersaturation and this allows one to explore the high metastable region without encountering the KS. On increasing the range of interaction, both the critical cluster size and pre-critical minima in the free energy surface of kth largest cluster, at respective kinetic spinodals, shift towards smaller cluster size. In order to separate surface tension contribution to the increase in the barrier from other non-trivial factors, we introduce a new scaling form for surface tension and use it to capture both the temperature and the interaction range dependence of surface tension. Surprisingly, we find only a weak non-trivial contribution from other factors to the free energy barrier of nucleation.     

Homogeneous operators and projective representations of the Möbius group: A survey

This paper surveys the existing literature on homogeneous operators and their relationships with projective representations ofPS L(2, ℝ) and other Lie groups. It also includes a list of open problems in this area.     

One-Pot Dual C−C Coupling Reaction via Site Selective Cascade Formation by PdII-Cryptate of an Amino-Ether Heteroditopic Macrobicycle

Selectivity of aryl iodo over ethynyl iodo toward the Suzuki cross coupling reaction is explored by utilizing a palladium complex of amino-ether heteroditopic macrobicycle. Subsequently, unreacted ethynyl iodide undergoes homocoupling reaction in the same catalytic atmosphere, thereby representing a cascade dual C−C coupling reaction. Furthermore, this approach is extended for novel one-pot synthesis of unsymmetrical 1,3-diynes.     

Supersymmetry and the ladder operator technique in quantum mechanics: The radial Schrödinger equation

Using the ladder operator technique, a construction of the supersymmetric Hamiltonian is proposed. We show that the accidental degeneracies associated with the Coulomb and isotropic oscillator problems may be attributed to the existence of a supersymmetry of the Hamiltonians.     

Experimental investigation of real-time scheduling in flexible manufacturing systems

This paper presents a new two-phase (TP) approximate method for real-time scheduling in a flexible manufacturing system (FMS). This method combines a reduced enumeration schedule generation algorithm with a 0–1 optimization algorithm. In order to make the combined algorithm practicable, heuristic rules are introduced for the selection of jobs to be scheduled. The relative performance of the TP method vis-a-vis conventional heuristic dispatching rules such as SPT, LPT, FCFS, MWKR, and LWKR is investigated using combined process-interaction/discrete-event simulation models. An efficient experimental procedure is designed and implemented using these models, and the statistical analysis of the results is presented. For the particular case investigated, the conclusions are very encouraging. In terms of mean flow time, the TP method performs significantly better than any other tested heuristic dispatching rules. Also, the experimental results show that using global information significantly improves the FMS performance.     

2-satisfiability and diagnosing faulty processors in massively parallel computing systems

A fault diagnosis model for multiprocessor computers is proposed. Under normal operating mode each processor executes its own data. When an error occurs, the system is switched to the diagnostic mode. Previous input data for each processor is shifted to a different unit, to obtain a set of comparison results. We show that analysis of the test data to diagnose or locate faulty processors is equivalent to a 2-satisfiability problem. Under the assumption that discrepancy in a comparison result occurs if and only if at least one of the processors (being compared) is faulty, we prove that all the faulty processors can be diagnosed in O(n²) time, where n denotes the number of processors in the system.     

Stochastic Games with Average Payoff Criterion

We study two-person stochastic games on a Polish state and compact action spaces and with average payoff criterion under a certain ergodicity condition. For the zero-sum game we establish the existence of a value and stationary optimal strategies for both players. For the nonzero-sum case the existence of Nash equilibrium in stationary strategies is established under certain separability conditions. Accepted 9 January 1997