1,721,197 research outputs found
Approximate Optimization of Low-Thrust Transfers Between Low-Eccentricity Close Orbits
No full textAn approximation of the optimal control law for low-thrust transfers between low-eccentricity orbits with small changes of orbital elements is introduced. Transfers with a small number of revolutions around the main body are considered; in this case, Edelbaum's approximation, which is commonly adopted to analyze longer missions, provides unsatisfactory results. The novel approach presented here allows for analytic integration of the differential equations which describe the change of the orbital elements. Numerical solution of an algebraic system provides the control law that is required to obtain the prescribed orbit change. Results for different test cases are shown in comparison to the exact optimal solutions obtained with an indirect method. The mission costs that are evaluated with the approximate control law, provide a very accurate estimation of the actual optima, with a computational cost which is orders of magnitude lowe
Pre-mRNA Splicing: An Evolutionary Computational Journey from Ribozymes to Spliceosome
Full text linkThe intron–exon organization of the genes is nowadays taken for granted and constitutes a fully established theory. DNA protein-coding sequences (exons) are not contiguous but rather separated by silent intervening fragments (introns), which must be removed in a process called pre-mRNA splicing. However, this fragmented composition of the eukaryotic genome has ancient origins. It appears that, during the initial stages of eukaryotic evolution, group II introns, i.e. self-splicing catalytic ribozymes, invaded the eukaryotic genome via the endosymbiosis of an alpha-proteobacterium in an archaeal host. At a later time, they split into the inert spliceosomal introns and the catalytically active small nuclear (sn)RNAs, which, together with additional splicing factors, gave rise to the eukaryotic spliceosome. This marked the transition from the autocatalytic splicing, mediated by ribozymes (RNA filaments endowed with an intrinsic catalytic activity) to splicing mediated by a protein-RNA machinery, the spliceosome.
In the present thesis, the evolutionary relationship between group II introns and the spliceosome is retraced from a computational perspective by means of classical molecular dynamics simulations (MD), quantum mechanics calculations (QM) and combined quantum-classical simulations (QM/MM). The splicing process of these two different – but mechanistically related – large and sophisticated biomolecules is investigated with the aim of deciphering the reactivity and the structural properties from a computational point of view, with a focus on the role played by the Mg2+ ions as splicing cofactors.
In Chapter 2, the importance of Mg2+ ions in the RNA biology is introduced. Not only they participate to the catalysis, but also represent essential structural and functional elements for RNA filaments. Moreover, the structural and molecular biology of group II intron ribozymes and the spliceosome machinery are widely discussed with a focus on their evolutionary links. Chapter 3 consists of a brief review of all the computational techniques employed in this thesis, from classical MD to QM and QM/MM simulations and enhanced sampling methods aimed at reconstructing the free energy of a process. Chapter 4 is entirely dedicated to the splicing mechanism promoted by group II intron ribozymes, representing the starting point of the evolutionary journey. In this chapter, a QM/MM study of the molecular mechanism of group II introns first-step hydrolytic splicing is presented, unveiling an RNA-adapted Steitz and Steitz’s two-Mg2+-ion dissociative catalysis which differs from the one observed in protein enzymes. Chapter 5 is focused on Mg2+ ions, which are the natural cofactors of splicing, both in group II introns and in the spliceosome. Mg2+/RNA interplay is here addressed using a group II intron as a prototype of a large RNA molecule binding Mg2+. The performances of five different force fields currently used to describe Mg2+ in MD simulations are benchmarked, showing strengths and drawbacks. Moreover, the non-trivial electronic effects induced by Mg2+ on its ligands, such as charge transfer and polarization, are also characterized using 16 recurrent binding motifs. Overall, the study offers some guidelines on Mg2+ force fields for users and developers. Chapter 6 represents the final stop of the evolutionary journey. Here, an exquisite cryo-EM model of the ILS spliceosomal complex solved at 3.6 Å resolution is used for a long-time scale MD study. This provides precious insights on the main proteins and snRNAs involved in the pre-mRNA splicing in eukaryotes as well as on the catalytic site. Unprecedentedly, the structural and dynamical properties of the spliceosome machinery are investigated at the atomistic level, with a particular emphasis on protein/RNA interplay through the characterization of their principal motions, among which the intron lariat/U2 snRNA helix unwinding
DESIGN OF LUNAR-GRAVITY-ASSISTED ESCAPE MANEUVERS
No full textLunar gravity assist is a means to boost the energy and C3 of an escape maneuver. Two approaches are applied and tested for the design of trajectories aimed at Near-Earth asteroids. Maneuvers with two lunar gravity assists are considered and analyzed. Indirect optimization of the heliocentric leg is combined to an approximate analytical treatment of the geocentric phase for short escape maneuvers. The results of pre-computed maps of escape C3 are used for the design of longer sun-perturbed escape sequences. Features are compared and suggestions about a combined use of the approaches are presented. The techniques are efficiently applied to the design of a mission to a near-Earth asteroid
Autonomous Phasing Maneuvers in Near Circular Earth Orbits
No full textAutonomous, reliable and efficient guidance systems for new small satellites al low for the development and implementation of missions and technologies, such as on orbit servicing, that would be crucial for the evolution of space sector. In this context, this work refers to the problem of impulsive reconfiguration of rel ative motion between a chaser active spacecraft and a target passive one, in near circular Earth orbits. This procedure searches for impulse magnitudes and cor responding times of application to reach an aimed final relative configuration, in a fixed time window, while minimizing propellant consumption. Relative orbital elements are chosen as state variables and closed form solutions are preferred over numerical methods, because of their predictability and computational efficiency. The proposed solutions are inspired from the AVANTI flight demonstration, but specific strategies to address the case in which the relative planar motion change is dominant in the along track direction (rephasing scenarios) are introduced here. The new strategies are compared to the ones used in the AVANTI demonstration
in different scenarios. Similar solutions are obtained for small changes of rela tive mean longitude, proving the flexibility of the new schemes. As expected, for scenarios with large along track changes, the new strategies specifically designed for these cases, outperform the original strategies (with δv savings almost always
above 50%). The optimality of the proposed solutions is checked by comparison with the actual global optimum found numerically. Results show that the δv is within 1% from the optimum in 95.3% of cases and always within 4.5%. The ul timate contribution of this work is to provide a simple and effective algorithm to evaluate the convenience to combine in-plane and out-of-plane maneuvers, along with general theoretical understanding of 3D reconfiguration
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