A conformational approach to the study of the dynamics of enzyme inhibition: studies on thermolysin

The preferred conformations of β-phenylpropionyl-Image -phenylalanine (β-PPP) and N-carbobenzoxy-L-phenylalanine (Cbz-Phe), two inhibitors of thermolysin, have been determined by computing potential energy using empirial potential energy functions. Of the 15 to 20 conformations that are favoured for each of these inhibitors only a few have the right conformation to reach the active site of the enzyme. The conformer of β-PPP that initiates binding with the enzyme is different from the bound one, while for Cbz-Phe the bound and initiating conformers are quite similar. Thus, β-PPP favours the ‘induced fit’ model while Cbz-Phe follows the ‘lock and key’ model of binding. The inhibitors differ in their alignment at the active site.

A Newton-Euler formulation for the inverse dynamics of the Stewart platform manipulator

This paper presents an inverse dynamic formulation by the Newton–Euler approach for the Stewart platform manipulator of the most general architecture and models all the dynamic and gravity effects as well as the viscous friction at the joints. It is shown that a proper elimination procedure results in a remarkably economical and fast algorithm for the solution of actuator forces, which makes the method quite suitable for on-line control purposes. In addition, the parallelism inherent in the manipulator and in the modelling makes the algorithm quite efficient in a parallel computing environment, where it can be made as fast as the corresponding formulation for the 6-dof serial manipulator. The formulation has been implemented in a program and has been used for a few trajectories planned for a test manipulator. Results of simulation presented in the paper reveal the nature of the variation of actuator forces in the Stewart platform and justify the dynamic modelling for control.

Fluid dynamics of the monsoon

The monsoonal regions of the world are characterized by a seasonal reversal in the direction of winds associated with the excursion of the equatorial trough (or the ITCZ) in response to the variation in the latitude of maximum insolation. This monsoonal circulation is a planetary scale phenomenon. However, the associated precipitation is critically dependent on the organization of the cumulus clouds (typically a few kilometers in horizontal extent) over the scale of synoptic vortices (typically a few hundred kilometers in horizontal extent). Thus modelling of the seasonal transitions and intraseasonal fluctuations requires an understanding of the fluid mechanics of these three scales of organizations and their interactions. The present paper is an attempt to outline the current state of understanding of these phenomena.

Dynamics of a class of social interaction systems

A mathematical model of social interaction in the form of two coupler! first-order non-linear differential equations, forms the topic of this study. This non-conservative model io representative of such varied social interaction problems as coexisting sub-populations of two different species, arms race between two rival countries and the like. Differential transformation techniques developed elsewhere in the literature are seen to be effective tools of dynamic analysis of this non-linear non-conservative mode! of social interaction process.

Dynamics of carbohydrateâlectin interaction The interaction p-nitrophenyl-β-D-galactose with a lectin from Ricinius communis

L&in-induced agglutination is a complex process determined by several factprs such as the nature of lectin (valency, binding constant) the properties of cell membrane (fluidity, distribution of lectin receptor sites) and the metabolic state of the cell (microvilli, microtubules, microfilament) [l-3].

Dynamics of Circulating Concentrations of Gonadotropins and Ovarian Hormones Throughout the Menstrual Cycle in the Bonnet Monkey: Role of Inhibin A in the Regulation of Follicle-Stimulating Hormone Secretion

In higher primates, increased circulating follicle-stimulating hormone (FSH) levels seen during late menstrual cycle and during menstruation has been suggested to be necessary for initiation of follicular growth, recruitment of follicles and eventually culminating in ovulation of a single follicle. With a view to establish the dynamics of circulating FSH secretion with that of inhibin A (INH A) and progesterone (P-4)secretions during the menstrual cycle, blood was collected daily from bonnet monkeys beginning day 1 of the menstrual cycle up to 35 days. Serum INH A levels were low during early follicular phase, increased significantly coinciding with the mid cycle luteinizing hormone (LH) surge to reach maximal levels during the mid luteal phase before declining at the late luteal phase, essentially paralleling the pattern Of P-4 secretion seen throughout the luteal phase. Circulating FSH levels were low during early and mid luteal phases, but progressively increased during the late luteal phase and remained high for few days after the onset of menses. In another experiment, lutectomy performed during the mid luteal phase resulted in significant decrease in INH A concentration within 2 hr (58.3 +/- 2 vs. 27.3 +/- 3 pg/mL), and a 2- to 3-fold rise in circulating FSH levels by 24 hr (0.20 +/- 0.02 vs. 0.53 +/- 0.14 ng/mL) that remained high until 48 hr postlutectomy. Systemic administration of Cetrorelix (150 mu g/kg body weight), a gonadotropin releasing hormone receptor antagonist, at mid luteal phase in monkeys led to suppression of serum INH A and P-4 concentrations 24 hr post treatment, but circulating FSH levels did not change. Administration of exogenous LH, but not FSH, significantly increased INH A concentration. The results taken together suggest a tight coupling between LH and INH A secretion and that INH A is largely responsible for maintenance of low FSH concentration seen during the luteal phase. Am. J. Primatol. 71:817-824, 2009.

Dissipative dynamics of a harmonic oscillator: A nonperturbative approach

Starting from a microscopic theory, we derive a master equation for a harmonic oscillator coupled to a bath of noninteracting oscillators. We follow a nonperturbative approach, proposed earlier by us for the free Brownian particle. The diffusion constants are calculated analytically and the positivity of the master equation is shown to hold above a critical temperature. We compare the long time behavior of the average kinetic and potential energies with known thermodynamic results. In the limit of vanishing oscillator frequency of the system, we recover the results of the free Brownian particle.

Entanglement production due to quench dynamics of an anisotropic XY chain in a transverse field

We compute concurrence and negativity as measures of two-spin entanglement generated by a power-law quench (characterized by a rate tau(-1) and an exponent alpha) which takes an anisotropic XY chain in a transverse field through a quantum critical point (QCP). We show that only spins separated by an even number of lattice spacings get entangled in such a process. Moreover, there is a critical rate of quench, tau(-1)(c), above which no two-spin entanglement is generated; the entire entanglement is multipartite. The ratio of the entanglements between consecutive even neighbors can be tuned by changing the quench rate. We also show that for large tau, the concurrence (negativity) scales as root alpha/tau(alpha/tau), and we relate this scaling behavior to defect production by the quench through a QCP.

Ligand dependent intra and inter subunit communication in human tryptophanyl tRNA synthetase as deduced from the dynamics of structure networks

Homodimeric protein tryptophanyl tRNA synthetase (TrpRS) has a Rossmann fold domain and belongs to the 1c subclass of aminoacyl tRNA synthetases. This enzyme performs the function of acylating the cognate tRNA. This process involves a number of molecules (2 protein subunits, 2 tRNAs and 2 activated Trps) and thus it is difficult to follow the complex steps in this process. Structures of human TrpRS complexed with certain ligands are available. Based on structural and biochemical data, mechanism of activation of Trp has been speculated. However, no structure has yet been solved in the presence of both the tRNA(Trp) and the activated Trp (TrpAMP). In this study, we have modeled the structure of human TrpRS bound to the activated ligand and the cognate tRNA. In addition, we have performed molecular dynamics (MD) simulations on these models as well as other complexes to capture the dynamical process of ligand induced conformational changes. We have analyzed both the local and global changes in the protein conformation from the protein structure network (PSN) of MD snapshots, by a method which was recently developed in our laboratory in the context of the functionally monomeric protein, methionyl tRNA synthetase. From these investigations, we obtain important information such as the ligand induced correlation between different residues of this protein, asymmetric binding of the ligands to the two subunits of the protein as seen in the crystal structure analysis, and the path of communication between the anticodon region and the aminoacylation site. Here we are able to elucidate the role of dimer interface at a level of detail, which has not been captured so far.

Buckling, stiffening, and negative dissipation in the dynamics of a biopolymer in an active medium

We present a generic theory for the dynamics of a stiff filament under tension, in an active medium with orientational correlations, such as a microtubule in contractile actin. In sharp contrast to the case of a passive medium, we find the filament can stiffen, and possibly oscillate or buckle, depending on both the contractile or tensile nature of the activity and the filament-medium anchoring interaction. We also demonstrate a strong violation of the fluctuation-dissipation (FD) relation in the effective dynamics of the filament, including a negative FD ratio. Our approach is also of relevance to the dynamics of axons, and our model equations bear a remarkable formal similarity to those in recent work [Martin P, Hudspeth AJ, Juelicher F (2001) Proc Natl Acad Sci USA 98: 14380-14385] on auditory hair cells. Detailed tests of our predictions can be made by using a single filament in actomyosin extracts or bacterial suspensions.

Dynamics of loop formation in a semiflexible polymer

The dynamics of loop formation by linear polymer chains has been a topic of several theoretical and experimental studies. Formation of loops and their opening are key processes in many important biological processes. Loop formation in flexible chains has been extensively studied by many groups. However, in the more realistic case of semiflexible polymers, not much results are available. In a recent study [K. P. Santo and K. L. Sebastian, Phys. Rev. E 73, 031923 (2006)], we investigated opening dynamics of semiflexible loops in the short chain limit and presented results for opening rates as a function of the length of the chain. We presented an approximate model for a semiflexible polymer in the rod limit based on a semiclassical expansion of the bending energy of the chain. The model provided an easy way to describe the dynamics. In this paper, using this model, we investigate the reverse process, i.e., the loop formation dynamics of a semiflexible polymer chain by describing the process as a diffusion-controlled reaction. We make use of the ``closure approximation'' of Wilemski and Fixman [G. Wilemski and M. Fixman, J. Chem. Phys. 60, 878 (1974)], in which a sink function is used to represent the reaction. We perform a detailed multidimensional analysis of the problem and calculate closing times for a semiflexible chain. We show that for short chains, the loop formation time tau decreases with the contour length of the polymer. But for longer chains, it increases with length obeying a power law and so it has a minimum at an intermediate length. In terms of dimensionless variables, the closing time is found to be given by tau similar to L-n exp(const/L), where n=4.5-6. The minimum loop formation time occurs at a length L-m of about 2.2-2.4. These are, indeed, the results that are physically expected, but a multidimensional analysis leading to these results does not seem to exist in the literature so far.

The dynamics of magnetically trapped fluids. I - Implications for umbral dots and penumbral grains

A study of the magnetohydrodynamic system in which a nonmagnetized fluid in a gravitational field is surrounded by a fluid carrying a vertical magnetic field is presented. It is pointed out that this study can throw some light on the fine-structural features of a sunspot. The equilibrium configuration of the field-free fluid is a tapering column ending at an apex. The regions away form the apex can be studied by the slender flux tube approximation. A scheme developed to treat the apex indicates that, just below the apex, the radius of the tapering column opens up with a 3/2 power dependence on the depth below the apex. If the internal pressure of the field-free fluid is increased, the apex rises, and a static equilibrium may not be possible beyond a limit if the magnetic pressure drops quickly above a certain height. The nature of steady-flow solutions beyond this limit is investigated. Under conditions inside a sunspot, a column of field-free gas is found to rise with a velocity of about 100 km/hr. If umbral dots and penumbral grains are interpreted as regions where the field-free gas ultimately emerges, a very natural explanation of most of their observed properties is obtained.

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.