Native geometry and the dynamics of protein folding

In this paper we investigate the role of native geometry on the kinetics of protein folding based on simple lattice models and Monte Carlo simulations. Results obtained within the scope of the Miyazawa-Jernigan indicate the existence of two dynamical folding regimes depending on the protein chain length. For chains larger than 80 amino acids the folding performance is sensitive to the native state's conformation. Smaller chains, with less than 80 amino acids, fold via two-state kinetics and exhibit a significant correlation between the contact order parameter and the logarithmic folding times. In particular, chains with N=48 amino acids were found to belong to two broad classes of folding, characterized by different cooperativity, depending on the contact order parameter. Preliminary results based on the G\={o} model show that the effect of long range contact interaction strength in the folding kinetics is largely dependent on the native state's geometry.Comment: Proceedings of the BIFI 2004 - I International Conference, Zaragoza (Spain) Biology after the genome: a physical view. To appear in Biophysical Chemistr

Rapid automatized naming and reading performance: a meta-analysis

Evidence that rapid naming skill is associated with reading ability has become increasingly prevalent in recent years. However, there is considerable variation in the literature concerning the magnitude of this relationship. The objective of the present study was to provide a comprehensive analysis of the evidence on the relationship between rapid automatized naming (RAN) and reading performance. To this end, we conducted a meta-analysis of the correlational relationship between these 2 constructs to (a) determine the overall strength of the RAN-reading association and (b) identify variables that systematically moderate this relationship. A random-effects model analysis of data from 137 studies (857 effect sizes; 28,826 participants) indicated a moderate-to-strong relationship between RAN and reading performance (r = .43, I-2 = 68.40). Further analyses revealed that RAN contributes to the 4 measures of reading (word reading, text reading, non-word reading, and reading comprehension), but higher coefficients emerged in favor of real word reading and text reading. RAN stimulus type and type of reading score were the factors with the greatest moderator effect on the magnitude of the RAN-reading relationship. The consistency of orthography and the subjects' grade level were also found to impact this relationship, although the effect was contingent on reading outcome. It was less evident whether the subjects' reading proficiency played a role in the relationship. Implications for future studies are discussed

Folding of small proteins: A matter of geometry?

We review some of our recent results obtained within the scope of simple lattice models and Monte Carlo simulations that illustrate the role of native geometry in the folding kinetics of two state folders.Comment: To appear in Molecular Physic

Numerical Modeling of River Diversions in the Lower Mississippi River

The presence of man-made levees along the Lower Mississippi River (MR) has significantly reduced the River sediment input to the wetlands and much of the River\u27s sediment is now lost to the Gulf of Mexico. The sediment load in the River has also been decreased by dams and river revetments along the Upper MR. Freshwater and sediment diversions are possible options to help combat land loss. Numerical modeling of hydrodynamics and sediment transport of the MR is a useful tool to evaluate restoration projects and to improve our understanding of the resulting River response. The emphasis of this study is on the fate of sand in the river and the distributaries. A 3-D unsteady flow mobile-bed model (ECOMSED; HydroQual 2002) of the Lower MR reach between Belle Chasse (RM 76) and downstream of Main Pass (RM 3) was calibrated using field sediment data from 2008 – 2010 (Nittrouer et al. 2008; Allison, 2010). The model was used to simulate River currents, diversion sand capture efficiency, erosional and depositional patterns with and without diversions over a short period of time (weeks). The introduction of new diversions at different locations, e.g., Myrtle Grove (RM 59) and Belair (RM 65), with different geometries and with different outflows was studied. A 1-D unsteady flow mobile-bed model (CHARIMA; Holly et al. 1990) was used to model the same Lower MR reach. This model was used for longer term simulations (months). The simulated diversions varied from 28 m3/s (1, 000 cfs) to 5, 700 m3/s (200, 000 cfs) for river flows up to 35, 000 m3/s (1.2x106 cfs). The model showed that the smaller diversions had little impact on the downstream sand transport. However, the larger diversions had the following effects: 1) reduction in the slope of the hydraulic grade line downstream of the diversion; 2) reduction in the available energy for transport of sand along distributary channels; 3) reduced sand transport capacity in the main channel downstream of the diversion; 4) increased shoaling downstream of the diversion; and 5) a tendency for erosion and possible head-cutting upstream of the diversion

Numerical Modeling of River Diversions in the Lower Mississippi River

The presence of man-made levees along the Lower Mississippi River (MR) has significantly reduced the River sediment input to the wetlands and much of the River\u27s sediment is now lost to the Gulf of Mexico. The sediment load in the River has also been decreased by dams and river revetments along the Upper MR. Freshwater and sediment diversions are possible options to help combat land loss. Numerical modeling of hydrodynamics and sediment transport of the MR is a useful tool to evaluate restoration projects and to improve our understanding of the resulting River response. The emphasis of this study is on the fate of sand in the river and the distributaries. A 3-D unsteady flow mobile-bed model (ECOMSED; HydroQual 2002) of the Lower MR reach between Belle Chasse (RM 76) and downstream of Main Pass (RM 3) was calibrated using field sediment data from 2008 – 2010 (Nittrouer et al. 2008; Allison, 2010). The model was used to simulate River currents, diversion sand capture efficiency, erosional and depositional patterns with and without diversions over a short period of time (weeks). The introduction of new diversions at different locations, e.g., Myrtle Grove (RM 59) and Belair (RM 65), with different geometries and with different outflows was studied. A 1-D unsteady flow mobile-bed model (CHARIMA; Holly et al. 1990) was used to model the same Lower MR reach. This model was used for longer term simulations (months). The simulated diversions varied from 28 m3/s (1, 000 cfs) to 5, 700 m3/s (200, 000 cfs) for river flows up to 35, 000 m3/s (1.2x106 cfs). The model showed that the smaller diversions had little impact on the downstream sand transport. However, the larger diversions had the following effects: 1) reduction in the slope of the hydraulic grade line downstream of the diversion; 2) reduction in the available energy for transport of sand along distributary channels; 3) reduced sand transport capacity in the main channel downstream of the diversion; 4) increased shoaling downstream of the diversion; and 5) a tendency for erosion and possible head-cutting upstream of the diversion

Cognitive subtyping of university students with dyslexia in a semi-transparent orthography: what can weaknesses and strengths tell us about compensation?

Developmental dyslexia is characterized by a profile of reading- and writing-related difficulties which stands out as a core deficit in phonological processing. Although these difficulties seem to persist into adulthood, it is still an open question to what extent they are immune, or not, to the extensive training resulting from extended schooling. The main objective of this study was to explore the heterogeneity of the cognitive profile of European Portuguese highly literate adults with dyslexia. Thirty-one university students diagnosed with dyslexia during childhood and their matched skilled adult control readers were assessed through a battery of reading and cognitive tests. A cluster analysis of data obtained from participants with dyslexia identified two profile groups. While Cluster 1 grouped participants with clear phonological deficits and concomitant reading difficulties, Cluster 2 showed better performance on most of the core skills associated with reading and also better general cognitive abilities, suggesting that these dyslexic readers have partially resolved their phonological constraints along the development, probably due to the systematic exposure to reading and writing. As Cluster 2 matched typical readers in general cognitive abilities, it might also be the case that cognitive strengths associated with general intelligence worked as protective factors, helping students to strategically compensate for their reading difficulties. Overall, these results suggest that both mechanisms-partial remediation of the core phonological deficit and adoption of compensatory strategies supported by general cognitive skills-might contribute together to improving the reading performance of highly literate adults with dyslexia.2021.03462.CEECIND; LA/P/0053/2020 RISEinfo:eu-repo/semantics/publishedVersio

How Difficult Is It to Fold a Knotted Protein? In Silico Insights from Surface-Tethered Folding Experiments

We explore the effect of surface tethering on the folding process of a lattice protein that contains a trefoil knot in its native structure via Monte Carlo simulations. We show that the outcome of the tethering experiment depends critically on which terminus is used to link the protein to a chemically inert plane. In particular, if surface tethering occurs at the bead that is closer to the knotted core the folding rate becomes exceedingly slow and the protein is not able to find the native structure in all the attempted folding trajectories. Such low folding efficiency is also apparent from the analysis of the probability of knot formation, pknot, as a function of nativeness. Indeed, pknot increases abruptly from ~0 to ~1 only when the protein has more than 80% of its native contacts formed, showing that a highly compact conformation must undergo substantial structural re-arrangement in order to get effectively knotted. When the protein is surface tethered by the bead that is placed more far away from the knotted core pknot is higher than in the other folding setups (including folding in the bulk), especially if conformations are highly native-like. These results show that the mobility of the terminus closest to the knotted core is critical for successful folding of trefoil proteins, which, in turn, highlights the importance of a knotting mechanism that is based on a threading movement of this terminus through a knotting loop. The results reported here predict that if this movement is blocked, knotting occurs via an alternative mechanism, the so-called spindle mechanism, which is prone to misfolding. Our simulations show that in the three considered folding setups the formation of the knot is typically a late event in the folding process. We discuss the implications of our findings for co-translational folding of knotted trefoils. © 2012 Soler, Faísca

Effects of Knots on Protein Folding Properties

This work explores the impact of knots, knot depth and motif of the threading terminus in protein folding properties (kinetics, thermodynamics and mechanism) via extensive Monte Carlo simulations of lattice models. A knotted backbone has no effect on protein thermodynamic stability but it may affect key aspects of folding kinetics. In this regard, we found clear evidence for a functional advantage of knots: knots enhance kinetic stability because a knotted protein unfolds at a distinctively slower rate than its unknotted counterpart. However, an increase in knot deepness does not necessarily lead to more effective changes in folding properties. In this regard, a terminus with a non-trivial conformation (e.g. hairpin) can have a more dramatic effect in enhancing kinetic stability than knot depth. Nevertheless, our results suggest that the probability of the denatured ensemble to keep knotted is higher for proteins with deeper knots, indicating that knot depth plays a role in determining the topology of the denatured state. Refolding simulations starting from denatured knotted conformations show that not every knot is able to nucleate folding and further indicate that the formation of the knotting loop is a key event in the folding of knotted trefoils. They also show that there are specific native contacts within the knotted core that are crucial to keep a native knotting loop in denatured conformations which otherwise have no detectable structure. The study of the knotting mechanism reveals that the threading of the knotting loop generally occurs towards late folding in conformations that exhibit a significant degree of structural consolidation. © 2013 Soler, Faísca