Protein Folding Simulations: Confinement, External Fields and Sequence Design

The present Thesis looks at the problem of protein folding using Monte Carlo and Langevin simulations, three topics in protein folding have been studied: 1) the effect of confining potential barriers, 2) the effect of a static external field and 3) the design of amino acid sequences which fold in a short time and which have a stable native state (global minimum). Regarding the first topic, we studied the confinement of a small protein of 16 amino acids known as 1NJ0 (PDB code) which has a beta-sheet structure as a native state. The confinement of proteins occurs frequently in the cell environment. Some molecules called Chaperones, present in the cytoplasm, capture the unfolded proteins in their interior and avoid the formation of aggregates and misfolded proteins. This mechanism of confinement mediated by Chaperones is not yet well understood. In the present work we considered two kinds of potential barriers which try to mimic the confinement induced by a Chaperon molecule. The first kind of potential was a purely repulsive barrier whose only effect is to create a cavity where the protein folds up correctly. The second kind of potential was a barrier which includes both attractive and repulsive effects. We performed Wang-Landau simulations to calculate the thermodynamical properties of 1NJ0. From the free energy landscape plot we found that 1NJ0 has two intermediate states in the bulk (without confinement) which are clearly separated from the native and the unfolded states. For the case of the purely repulsive barrier we found that the intermediate states get closer to each other in the free energy landscape plot and eventually they collapse into a single intermediate state. The unfolded state is more compact, compared to that in the bulk, as the size of the barrier decreases. For an attractive barrier modifications of the states (native, unfolded and intermediates) are observed depending on the degree of attraction between the protein and the walls of the barrier. The strength of the attraction is measured by the parameter $\epsilon$. A purely repulsive barrier is obtained for $\epsilon=0$ and a purely attractive barrier for $\epsilon=1$. The states are changed slightly for magnitudes of the attraction up to $\epsilon=0.4$. The disappearance of the intermediate states of 1NJ0 is already observed for $\epsilon =0.6$. A very high attractive barrier ($\epsilon \sim 1.0$) produces a completely denatured state. In the second topic of this Thesis we dealt with the interaction of a protein with an external electric field. We demonstrated by means of computer simulations, specifically by using the Wang-Landau algorithm, that the folded, unfolded, and intermediate states can be modified by means of a field. We have found that an external field can induce several modifications in the thermodynamics of these states: for relatively low magnitudes of the field ($<2.06 \times 10^8$ V/m) no major changes in the states are observed. However, for higher magnitudes than ($6.19 \times 10^8$ V/m) one observes the appearance of a new native state which exhibits a helix-like structure. In contrast, the original native state is a $\beta$-sheet structure. In the new native state all the dipoles in the backbone structure are aligned parallel to the field. The design of amino acid sequences constitutes the third topic of the present work. We have tested the Rate of Convergence criterion proposed by D. Gridnev and M. Garcia ({\it work unpublished}). We applied it to the study of off-lattice models. The Rate of Convergence criterion is used to decide if a certain sequence will fold up correctly within a relatively short time. Before the present work, the common way to decide if a certain sequence was a good/bad folder was by performing the whole dynamics until the sequence got its native state (if it existed), or by studying the curvature of the potential energy surface. There are some difficulties in the last two approaches. In the first approach, performing the complete dynamics for hundreds of sequences is a rather challenging task because of the CPU time needed. In the second approach, calculating the curvature of the potential energy surface is possible only for very smooth surfaces. The Rate of Convergence criterion seems to avoid the previous difficulties. With this criterion one does not need to perform the complete dynamics to find the good and bad sequences. Also, the criterion does not depend on the kind of force field used and therefore it can be used even for very rugged energy surfaces.

CD-Systems of Stateless Deterministic R(1)-Automata Governed by an External Pushdown Store

We study cooperating distributed systems (CD-systems) of stateless deterministic restarting automata with window size 1 that are governed by an external pushdown store. In this way we obtain an automata-theoretical characterization for the class of context-free trace languages.

A storage scheme for an automated archive

Presentation given at the Al-Azhar Engineering First Conference, AEC’89, Dec. 9-12 1989, Cairo, Egypt. The paper presented at AEC'89 suggests an infinite storage scheme divided into one volume which is online and an arbitrary number of off-line volumes arranged into a linear chain which hold records which haven't been accessed recently. The online volume holds the records in sorted order (e.g. as a B-tree) and contains shortest prefixes of keys of records already pushed offline. As new records enter, older ones are retired to the first volume which is going offline next. Statistical arguments are given for the rate at which an off-line volume needs to be fetched to reload a record which had been retired before. The rate depends on the distribution of access probabilities as a function of time. Applications are medical records, production records or other data which need to be kept for a long time for legal reasons.

Automated Reasoning About Classical Mechanics

In recent years, researchers in artificial intelligence have become interested in replicating human physical reasoning talents in computers. One of the most important skills in this area is predicting how physical systems will behave. This thesis discusses an implemented program that generates algebraic descriptions of how systems of rigid bodies evolve over time. Discussion about the design of this program identifies a physical reasoning paradigm and knowledge representation approach based on mathematical model construction and algebraic reasoning. This paradigm offers several advantages over methods that have become popular in the field, and seems promising for reasoning about a wide variety of classical mechanics problems.

Relative Contributions of Internal and External Features to Face Recognition

The central challenge in face recognition lies in understanding the role different facial features play in our judgments of identity. Notable in this regard are the relative contributions of the internal (eyes, nose and mouth) and external (hair and jaw-line) features. Past studies that have investigated this issue have typically used high-resolution images or good-quality line drawings as facial stimuli. The results obtained are therefore most relevant for understanding the identification of faces at close range. However, given that real-world viewing conditions are rarely optimal, it is also important to know how image degradations, such as loss of resolution caused by large viewing distances, influence our ability to use internal and external features. Here, we report experiments designed to address this issue. Our data characterize how the relative contributions of internal and external features change as a function of image resolution. While we replicated results of previous studies that have shown internal features of familiar faces to be more useful for recognition than external features at high resolution, we found that the two feature sets reverse in importance as resolution decreases. These results suggest that the visual system uses a highly non-linear cue-fusion strategy in combining internal and external features along the dimension of image resolution and that the configural cues that relate the two feature sets play an important role in judgments of facial identity.

SAGA: System for Automated Geographical Analysis [abstract]

SAGA (System for Automated Geographic Analysis) es un SIG libre con capacidades para el manejo y análisis de información tanto vectorial como ráster, con un especial enfoque en esta última. Asimismo, es su enfoque analítico el que constituye su característica más destacable, siendo una herramienta de primer orden para la extracción de información a partir de todo tipo de capas de datos georeferenciados. (...)

A First approximation to the realism/idealism debate about the external world

El text intenta fer una primera aproximació al debat contemporani entre realistes i anti-realistes sobre el món empíric, centrant-se en les posicions de Putnam i Nagel. El seu objectiu principal és el d'entendre les motivacions de les posicions i l'estructura actual del debat, i el d'establir les característiques que hauria de tenir qualsevol posició satisfactòria

Posicionando Digital.CSIC como un elemento clave en el Sistema de Gestión de la Información Científica del CSIC

Primera conferencia. Bibliotecas y Repositorios Digitales: Gestión del Conocimiento, Acceso Abierto y Visibilidad Latinoamericana. (BIREDIAL) Mayo 9 al 11 de 2011. Bogotá, Colombia.

Automated Reasoning II

Resolution over FOPL

Los equipos de orientación del sector : funciones y modelos de intervención = External guidance services : functions and intervention models.

Resumen basado en el del autor

Evaluating the performance of external fault ridethrough solutions used in wind farms with fixed speed induction generators when facing unbalanced faults

Na sequência da integração da energia eólica em larga escala foram estabelecidos códigos de rede pelos vários operadores de sistema, exigindo que os parques eólicos permaneçam em serviço durante e após a ocorrência de defeitos na rede a montante. Nos parques eólicos equipados com sistemas de velocidade constante este requisito pode ser assegurado pela instalação, no ponto de interligação à rede, de equipamento de compensação dinâmica de potência reactiva, controlado como fonte de tensão, sendo as funções de controlo baseadas em medidas efectuadas no ponto de interligação relativamente às componentes directas da tensão e da corrente. Como a adopção deste tipo de soluções externas é adequada ao funcionamento do sistema em regime equilibrado, este artigo foca a avaliação do desempenho da solução no caso da ocorrência de defeitos assimétricos. Os resultados obtidos através das simulações dinâmicas evidenciam o aparecimento de sobre tensões nas fases não afectadas pelo defeito que poderão colocar o parque eólico fora de serviço.

Validation of an automated algorithm for auditory brainstem response testing

This paper discusses the auditory brainstem response (ABR) testing for infants.