AMOEBA model

It is has been known that the atomic multipole moments for atoms in AMOEBA model can be calculated through quantum mechanics method and Stone s distributed multipole analysis [61]. Thus, it is straightforward to obtain the parameters of electric multipole potentials based on the distributed multipole analysis after the EMP sites of Gay-Berne particles are decided or directly from AMOEBA force field. However, the EMP parameters of Gay-Berne particles need to be optimized because they are derived based on the gas-phase ab initio quantum mechanics. One possible solution would be to match GBEMP and AMOEBA results for the electrostatic energies between CG particles and water molecules, or between CG particle dimers, at various separations and/or in different orientations. 

Ren P, Ponder JW (2003) Temperature and pressure dependence of AMOEBA water model. J Phys Chem B 107 5933... 

Robust, multimethod regression codes are required to optimize the rate parameters, also in view of possible strong correlations. For example, the BURENL routine, specifically developed for regression analysis of kinetic schemes (Donati and Buzzi-Ferraris, 1974 Villa et al., 1985) has been used in the case of SCR modeling activities. The adaptive simplex optimization method Amoeba was used for minimization of the objective function Eq. (35) when evaluating kinetic parameters for NSRC and DOC. 

A variety of mammalian cellular systems have been used as experimental models for documenting the in vitro effects of cannabinoids on immune responsiveness to viruses, bacteria, and amoebae. Blevins and Dumic (1980) indicated that THC had a protective effect against HSV infection in vitro. It was found that both HSV-1 and HSV-2 failed to replicate and produce extensive cytopathic effect (c.p.e.) in human cell monolayer cultures exposed before infection, at infection, or post infection to various concentrations of THC. In contrast, other studies indicate that THC compromises resistance to virus infection. It has been reported that THC inhibits macrophage extrinsic anti-viral activity (Cabral and Vasquez 1991 Cabral and Vdsquez 1992) whereby macrophages normally suppress virus replication in cells to which they attach (Morahan et al. 1980 Stohlman et al. 1982). Noe et al. (1998) reported that a variety of cannabinoid receptor agonists enhanced syncytia formation in human T cell leukemia virus-I (HTLV-I)-transformed human T (MT-2) cells infected with cell free human immunodeficiency virus (HIV-IMN). It was found that CP 55,940, THC, WIN 55,212-2, and WIN 55,212-3 significantly increased syncytia formation, a phenomenon that has been reported to serve as an indicator of HIV infection and cytopathicity. 

A. Levchenko, P.A. Iglesias, Models of eukaryotic gradient sensing application to chemotaxis of amoebae and neutrophils, Biophys. J. 2002, 82, 50-63. 

The ereation of a homoclinic orbit thus gives rise to a sharp decline in the munber of peaks within a burst. The abrupt transition from the bursting pattern with 11 peaks per period, ir(ll), to the pattern with 7 peaks, tt(7), in table 4.4 originates from the appearance of such a homoclinic orbit. It should be noted that the situation depicted in fig. 4.19e creates conditions suitable for the coexistence between bursting oscillations and a limit cycle that would be stabilized around a value of a between a and a. Such a situation is indeed close to that described further in chapter 6 for the origin of birhythmicity of a similar kind in a model for the intercellular communication system of Dictyostelium amoebae. 

As shown in the following chapters, the study of simple and complex oscillations in the signalling system used by Dictyostelium discoideum amoebae for intercellular communication confirms the general significance of the results established for the multiply regulated biochemical system. This model thus represents a three-variable prototype for analysing the transition from simple to complex oscillations in biochemical and cellular systems. 

Models for the periodic synthesis and relay of cAMP signals in Dictyostelium discoideum amoebae... 

The possible occurrence in the Dictyostelium system of complex oscillatory phenomena such as birhythmicity, bursting and chaos is discussed in chapter 6. The appearance of periodic behaviour in the course of development provides a model for the ontogenesis of biological rhythms. This aspect is treated in chapter 7. Finally, an additional interest of the intercellular communication system of Dictyostelium amoebae is that it allows us to address the question of the physiological function of the periodic phenomenon. This question is dealt with in chapter 8, where the discussion is extended to the role of pulsatile hormone secretion in higher organisms. 

The above observations account for the periodic secretion and relay of cAMP signals in the course of aggregation of amoebae on agar. The question which now arises is how to determine the molecular mechanism responsible for these two modes of dynamic behaviour. The theoretical study of experimentally based models clarifies the origin of relay and oscillations and permits us to explain why certain cells behave as centres while other cells act just as relays in the course of aggregation. 

Fig. 5.16. Allosteric model for cAMP synthesis in D. discoideum amoebae. Extracellular cAMP binds to the receptor (R) and activates adenylate cyclase (C), which transforms substrate ATP into intracellular cAMP. Arrows denote the synthesis of ATP, the transport of cAMP across the membrane into the extracellular medium, and cAMP hydrolysis by phosphodiesterase (Goldbeter Segel, 1977).

Such pulsatory amplification of the extracellular cAMP pulse accounts for the phenomenon of relay of cAMP signals observed during aggregation of the amoebae on agar (Robertson Drage, 1975) as well as in experiments in cell suspensions (Roos et al, 1975 see fig. 5.14). Table 5.1 shows that the qualitative and quantitative predictions of the model regarding relay behaviour yield satisfactory agreement with experimental observations. 

Despite its necessarily incomplete nature, it appears that the model analysed above for the synthesis of cAMP in D. discoideum amoebae is based on the most conspicuous properties of the signalling system, namely self-amplification due to the activation of adenylate cyclase that follows the binding of cAMP to the receptor, and desensitization of this receptor through cAMP-induced phosphorylation. 

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