Simulation, Experiment, and Evolution: Understanding Nucleation in Protein S6 Folding

In this study, we explore nucleation and the transition state ensemble of the ribosomal protein S6 using a Monte Carlo Go model in conjunction with restraints from experiment. The results are analyzed in the context of extensive experimental and evolutionary data. The roles of individual residues in the folding nucleus are identified and the order of events in the S6 folding mechanism is explored in detail. Interpretation of our results agrees with, and extends the utility of, experiments that shift f-values by modulating denaturant concentration and presents strong evidence for the realism of the mechanistic details in our Monte Carlo Go model and the structural interpretation of experimental f-values. We also observe plasticity in the contacts of the hydrophobic core that support the specific nucleus. For S6, which binds to RNA and protein after folding, this plasticity may result from the conformational flexibility required to achieve biological function. These results present a theoretical and conceptual picture that is relevant in understanding the mechanism of nucleation in protein folding.Comment: PNAS in pres

Principals of the theory of light reflection and absorption by low-dimensional semiconductor objects in quantizing magnetic fields at monochromatic and pulse excitations

The bases of the theory of light reflection and absorption by low-dimensional semiconductor objects (quantum wells, wires and dots) at both monochromatic and pulse irradiations and at any form of light pulses are developed. The semiconductor object may be placed in a stationary quantizing magnetic field. As an example the case of normal light incidence on a quantum well surface is considered. The width of the quantum well may be comparable to the light wave length and number of energy levels of electronic excitations is arbitrary. For Fourier-components of electric fields the integral equation (similar to the Dyson-equation) and solutions of this equation for some individual cases are obtained.Comment: 14 page

High resolution protein folding with a transferable potential

A generalized computational method for folding proteins with a fully transferable potential and geometrically realistic all-atom model is presented and tested on seven different helix bundle proteins. The protocol, which includes graph-theoretical analysis of the ensemble of resulting folded conformations, was systematically applied and consistently produced structure predictions of approximately 3 Angstroms without any knowledge of the native state. To measure and understand the significance of the results, extensive control simulations were conducted. Graph theoretic analysis provides a means for systematically identifying the native fold and provides physical insight, conceptually linking the results to modern theoretical views of protein folding. In addition to presenting a method for prediction of structure and folding mechanism, our model suggests that a accurate all-atom amino acid representation coupled with a physically reasonable atomic interaction potential (that does not require optimization to the test set) and hydrogen bonding are essential features for a realistic protein model.Comment: submitted to PNAS 2005-03-1

Variation in nucleotide homology obtained by amplification, cloning and sequencing of complete S1 gene from field samples of avian infectious bronchitis virus.

Projeto/Plano de Ação: 02.09.01.030

British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults

\ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service

Norm reasoning services

Norms are used in open Multi-Agent Systems as a formal specification of deontic statements aimed at regulating the actions of agents and the interactions among them. In this paper, we propose a set of services facilitating the development of both non-normative and normative agents for norm-governed MAS. Specifically, we propose to provide agents with norm reasoning services. These services will help agent designers/developers to programme agents that consider norm reasoning without having to implement the needed mechanisms to reason about norms by themselves. This article shows how these services perform as well as the results of the experiments that we conducted to evaluate their performance