Hot-spot analysis for drug discovery targeting protein-protein interactions

Introduction: Protein-protein interactions are important for biological processes and pathological situations, and are attractive targets for drug discovery. However, rational drug design targeting protein-protein interactions is still highly challenging. Hot-spot residues are seen as the best option to target such interactions, but their identification requires detailed structural and energetic characterization, which is only available for a tiny fraction of protein interactions. Areas covered: In this review, the authors cover a variety of computational methods that have been reported for the energetic analysis of protein-protein interfaces in search of hot-spots, and the structural modeling of protein-protein complexes by docking. This can help to rationalize the discovery of small-molecule inhibitors of protein-protein interfaces of therapeutic interest. Computational analysis and docking can help to locate the interface, molecular dynamics can be used to find suitable cavities, and hot-spot predictions can focus the search for inhibitors of protein-protein interactions. Expert opinion: A major difficulty for applying rational drug design methods to protein-protein interactions is that in the majority of cases the complex structure is not available. Fortunately, computational docking can complement experimental data. An interesting aspect to explore in the future is the integration of these strategies for targeting PPIs with large-scale mutational analysis.This work has been funded by grants BIO2016-79930-R and SEV-2015-0493 from the Spanish Ministry of Economy, Industry and Competitiveness, and grant EFA086/15 from EU Interreg V POCTEFA. M Rosell is supported by an FPI fellowship from the Severo Ochoa program. The authors are grateful for the support of the the Joint BSC-CRG-IRB Programme in Computational Biology.Peer ReviewedPostprint (author's final draft

DSP based platform for an enhanced HF channel simulator

With the aim of improving existing tools for testing new HF transmission systems, this article describes a modification of the basic Watterson (1970) model which can be implemented without any extra added complexity with a general purpose DSP card running an a PC IBM compatible.Peer ReviewedPostprint (published version

A shape optimization problem for Steklov eigenvalues in oscillating domains

In this paper we study the asymptotic behavior of some optimal design problems related to nonlinear Steklov eigenvalues, under irregular (but diffeomorphic) perturbations of the domain.Comment: Some typos fixe

Development and implementation of an adaptive digital beamforming network for satellite communication systems

The use of adaptive digital beamforming techniques has, until recently, been largely restricted to high performance military radar systems. Recent advances in digital technology, however, have enabled the design of single chip digital beamforming networks. This, coupled with advances in digital signal processor technology, enables complete beamforming systems to be constructed at a lower cost, thus making the application of these techniques to commercial communications systems attractive. The design and development of such an adaptative digital beamforming network are described. The system is being developed as a proof of concept laboratory based demonstrator to enable the feasibility of adaptive digital beamforming techniques for communication systems to be determined. Ultimately, digital beamforming could be used in conjunction with large array antennas for communication satellite systems. This will enable the simultaneous steering of high gain antenna beams in the direction of gr...Peer ReviewedPostprint (published version

Performance analysis of a hybrid ARQ system in half duplex transmission at 2400 BPS

Hybrid ARQ/FEC protocols have been proposed to provide high data link integrities whilst keeping at the same time a high mean throughput rate. Nevertheless, hybrid ARQ strategies offer a lot of choices and none of them can be considered the optimum in any case. Three alternative protocol strategies using BCH codes are evaluated and the HF channel models used for the tests are discussed.Peer ReviewedPostprint (published version

Path-integral Monte Carlo and the squeezed trapped Bose-Einstein gas

Bose-Einstein condensation has been experimentally found to take place in finite trapped systems when one of the confining frequencies is increased until the gas becomes effectively two-dimensional (2D). We confirm the plausibility of this result by performing path-integral Monte Carlo (PIMC) simulations of trapped Bose gases of increasing anisotropy and comparing them to the predictions of finite-temperature many-body theory. PIMC simulations provide an essentially exact description of these systems; they yield the density profile directly and provide two different estimates for the condensate fraction. For the ideal gas, we find that the PIMC column density of the squeezed gas corresponds quite accurately to that of the exact analytic solution and, moreover, is well mimicked by the density of a 2D gas at the same temperature; the two estimates for the condensate fraction bracket the exact result. For the interacting case, we find 2D Hartree-Fock solutions whose density profiles coincide quite well with the PIMC column densities and whose predictions for the condensate fraction are again bracketed by the PIMC estimates.Comment: 2 pages, 3 figure

Beamforming and Multiuser Detection in CDMA Systems with External Interferences

Multiuser detection has been investigated to mitigate the near-far effect in CDMA systems. Antenna arrays have been shown to provide spatial diversity and cancel undesired signals. In this paper we consider the synergy of both multiuser detection and antenna arrays for the base station of a CDMA system. The receiver we proposed consists of the known multiuser decorrelator, which cancels multiple-access interferences followed by a beamformer for each user, which cancels the external interferences. This receiver adds an extra branch to the decorrelator. This additional branch, corresponding to a fictitious user with an unused code and zero power, allows to estimate the external interference signal subspace and compute a suitable beamforming weight-vector that cancels the external interferences. The receiver is also extended to the asynchronous case and all of this without any training signal or any a priori spatial information.Peer ReviewedPostprint (published version