Properties of low-dimensional collective variables in the molecular dynamics of biopolymers

The description of the dynamics of a complex, high-dimensional system in terms of a low-dimensional set of collective variables Y can be fruitful if the low dimensional representation satisfies a Langevin equation with drift and diffusion coefficients which depend only on Y. We present a computational scheme to evaluate whether a given collective variable provides a faithful low-dimensional representation of the dynamics of a high-dimensional system. The scheme is based on the framework of finite-difference Langevin-equation, similar to that used for molecular-dynamics simulations. This allows one to calculate the drift and diffusion coefficients in any point of the full-dimensional system. The width of the distribution of drift and diffusion coefficients in an ensemble of microscopic points at the same value of Y indicates to which extent the dynamics of Y is described by a simple Langevin equation. Using a simple protein model we show that collective variables often used to describe biopolymers display a non-negligible width both in the drift and in the diffusion coefficients. We also show that the associated effective force is compatible with the equilibrium free--energy calculated from a microscopic sampling, but results in markedly different dynamical properties

Statistical Analysis of Native Contact Formation in the Folding of Designed Model Proteins

The time evolution of the formation probability of native bonds has been studied for designed sequences which fold fast into the native conformation. From this analysis a clear hierarchy of bonds emerge a) local, fast forming highly stable native bonds built by some of the most strongly interacting amino acids of the protein, b) non-local bonds formed late in the folding process, in coincidence with the folding nucleus, and involving essentially the same strongly interacting amino acids already participating in the fast bonds, c) the rest of the native bonds whose behaviour is subordinated, to a large extent, to that of the local- and non-local native contacts

Metadynamic sampling of the free energy landscapes of proteins coupled with a Monte Carlo algorithm

Metadynamics is a powerful computational tool to obtain the free energy landscape of complex systems. The Monte Carlo algorithm has proven useful to calculate thermodynamic quantities associated with simplified models of proteins, and thus to gain an ever-increasing understanding on the general principles underlying the mechanism of protein folding. We show that it is possible to couple metadynamics and Monte Carlo algorithms to obtain the free energy of model proteins in a way which is computationally very economical.Comment: Submitted to Gen

Cosmopolitanism and Global Justice: A Review Essay of Cosmopolitan Regard by Richard Vernon

While geologists may not be able to find physical proof to suggest that the world is shrinking, social scientists are convinced that this is the case. The amount of information that is shared amongst the world\u27s citizens has grown exponentially over the years, and evidence of an increasingly interconnected world can be seen in every facet of our everyday lives from the food we eat to what we watch on television. Thousands of miles that once divided us from one another are now eliminated by telephones, the Internet, and even the ability to make telephone calls over the Internet. In countries where people lack food security and safe drinking water, they are able to own a pre-paid cell phone and drink Coca-Cola. This is troubling for those who examine the world we live in today with all of its technological advancements and wonder why there are still over a billion people living below the poverty line. If the world is becoming one global village then why is there such a disparity between the Haves and the Have Nots? Some believe that it is the responsibility of those who have to improve the wellbeing of those who do not. In the book Cosmopolitan Regard, Political Membership and Global Justice, author Richard Vernon explains the importance of a cosmopolitan world and implications for the world\u27s citizens in its implementation

Selection On Different Genes With Equivalent Functions: The Convergence Story Told By Hox Genes Along The Evolution Of Aquatic Mammalian Lineages

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Convergent evolution has been a challenging topic for decades, being cetaceans, pinnipeds and sirenians textbook examples of three independent origins of equivalent phenotypes. These mammalian lineages acquired similar anatomical features correlated to an aquatic life, and remarkably differ from their terrestrial counterparts. Whether their molecular evolutionary history also involved similar genetic mechanisms underlying such morphological convergence nevertheless remained unknown. To test for the existence of convergent molecular signatures, we studied the molecular evolution of Hox genes in these three aquatic mammalian lineages, comparing their patterns to terrestrial mammals. Hox genes are transcription factors that play a pivotal role in specifying embryonic regional identity of nearly any bilateral animal, and are recognized major agents for diversification of body plans. Results: We detected few signatures of positive selection on Hox genes across the three aquatic mammalian lineages and verified that purifying selection prevails in these sequences, as expected for pleiotropic genes. Genes found as being positively selected differ across the aquatic mammalian lineages, but we identified a substantial overlap of their developmental functions. Such pattern likely resides on the duplication history of Hox genes, which probably provided different possible evolutionary routes for achieving the same phenotypic solution. Conclusions: Our results indicate that convergence occurred at a functional level of Hox genes along three independent origins of aquatic mammals. This conclusion reinforces the idea that different changes in developmental genes may lead to similar phenotypes, probably due to the redundancy provided by the participation of Hox paralogous genes in several developmental functions.16Ciencia sem Fronteiras - Atracao de Jovens Talentos CAPES [054/2012]FAPESP-Brazil [2010/52316-3]CNPq-Brazil [563232/2010-2]Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

RESOURCES AND QUALITY OF LIFE IN CAREGIVERS OF CHILDREN WITH AUTISM SPECTRUM DISORDER

Participants were 23 caregivers of children between the ages of four to twenty-two years old who are diagnosed with autism spectrum disorder and attend the Autism Society of North Carolina (ASNC) Social Recreation program in Winterville, Wilmington, and Newport. The present study evaluated the quality of life in parents of children with autism spectrum disorder, as well as the utilization and availability of resources for their child and the family. Data was collected using an online Qualtrics survey sent out to families by email. The survey consisted of questions regarding demographics, questions from the Questionnaire for Each Treatment regarding the treatments their child with autism receives, and questions from the Family Quality of Life Scale by the Beach Center on Disability. Overall results revealed that parenting is the most satisfying domain of quality of life, and disability related support was the least satisfactory for the parents. Results suggest that families with disability need to identify and enroll their children in early intervention programs and recreation program that help with children’s development. The government and school programs should also strive to offer educative sessions for parents and families with children with autism to enhance their contribution outside of school hours

What thermodynamic features characterize good and bad folders? Results from a simplified off-lattice protein model

The thermodynamics of the small SH3 protein domain is studied by means of a simplified model where each bead-like amino acid interacts with the others through a contact potential controlled by a 20x20 random matrix. Good folding sequences, characterized by a low native energy, display three main thermodynamical phases, namely a coil-like phase, an unfolded globule and a folded phase (plus other two phases, namely frozen and random coil, populated only at extremes temperatures). Interestingly, the unfolded globule has some regions already structured. Poorly designed sequences, on the other hand, display a wide transition from the random coil to a frozen state. The comparison with the analytic theory of heteropolymers is discussed

RESOURCES AND QUALITY OF LIFE IN CAREGIVERS OF CHILDREN WITH AUTISM SPECTRUM DISORDER

Participants were 23 caregivers of children between the ages of four to twenty-two years old who are diagnosed with autism spectrum disorder and attend the Autism Society of North Carolina (ASNC) Social Recreation program in Winterville, Wilmington, and Newport. The present study evaluated the quality of life in parents of children with autism spectrum disorder, as well as the utilization and availability of resources for their child and the family. Data was collected using an online Qualtrics survey sent out to families by email. The survey consisted of questions regarding demographics, questions from the Questionnaire for Each Treatment regarding the treatments their child with autism receives, and questions from the Family Quality of Life Scale by the Beach Center on Disability. Overall results revealed that parenting is the most satisfying domain of quality of life, and disability related support was the least satisfactory for the parents. Results suggest that families with disability need to identify and enroll their children in early intervention programs and recreation program that help with children’s development. The government and school programs should also strive to offer educative sessions for parents and families with children with autism to enhance their contribution outside of school hours