PubMed Health⌕ Search

PubMed · 15093836

Structure, function and evolution of multidomain proteins.

Abstract

Proteins are composed of evolutionary units called domains; the majority of proteins consist of at least two domains. These domains and nature of their interactions determine the function of the protein. The roles that combinations of domains play in the formation of the protein repertoire have been found by analysis of domain assignments to genome sequences. Additional findings on the geometry of domains have been gained from examination of three-dimensional protein structures. Future work will require a domain-centric functional classification scheme and efforts to determine structures of domain combinations.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Christine Vogel, Matthew Bashton, Nicola D Kerrison, Cyrus Chothia, Sarah A Teichmann. 2004. Structure, function and evolution of multidomain proteins.. https://doi.org/10.1016/j.sbi.2004.03.011

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Generating correlated data for omics simulation.

Simulation of realistic omics data is a key input for benchmarking studies that help users obtain optimal computational pipelines. Omics data involves large numbers of measured features on each sample and these measures are generally correlated with each other. However, simulation too often ignores these correlations, perhaps due to computational and statistical hurdles of doing so. To alleviate this, we describe three approaches for generating omics-scale data with correlated measures which mimic real datasets. These approaches are all based on a Gaussian copula approach with a covariance matrix that decomposes into a diagonal part and a low-rank part. This decomposition allows for extremely efficient simulation, overcoming a hurdle for adoption of past methods. We use these approaches to demonstrate the importance of including correlation in two benchmarking applications. First, we show that variance of results from the popular DESeq2 method increases when dependence is included. Second, we demonstrate that CYCLOPS, a method for inferring circadian time of collection from transcriptomics, improves in performance when given gene-gene dependencies in some circumstances. We provide an R package, dependentsimr, that has efficient implementations of these methods and can generate dependent data with arbitrary marginal distributions, including discrete (binary, ordered categorical, Poisson, negative binomial), continuous (normal), or with an empirical distribution.

Computer Simulation↗

Addressing current challenges in cancer immunotherapy with mathematical and computational modelling.

The goal of cancer immunotherapy is to boost a patient's immune response to a tumour. Yet, the design of an effective immunotherapy is complicated by various factors, including a potentially immunosuppressive tumour microenvironment, immune-modulating effects of conventional treatments and therapy-related toxicities. These complexities can be incorporated into mathematical and computational models of cancer immunotherapy that can then be used to aid in rational therapy design. In this review, we survey modelling approaches under the umbrella of the major challenges facing immunotherapy development, which encompass tumour classification, optimal treatment scheduling and combination therapy design. Although overlapping, each challenge has presented unique opportunities for modellers to make contributions using analytical and numerical analysis of model outcomes, as well as optimization algorithms. We discuss several examples of models that have grown in complexity as more biological information has become available, showcasing how model development is a dynamic process interlinked with the rapid advances in tumour-immune biology. We conclude the review with recommendations for modellers both with respect to methodology and biological direction that might help keep modellers at the forefront of cancer immunotherapy development.

Computer Simulation↗

Improved confidence intervals for the sensitivity at a fixed level of specificity of a continuous-scale diagnostic test.

For a continuous-scale diagnostic test, it is of interest to construct a confidence interval for the sensitivity of the diagnostic test at the cut-off that yields a predetermined level of its specificity (for example, 80, 90 or 95 per cent). In this paper we propose two new intervals for the sensitivity of a continuous-scale diagnostic test at a fixed level of specificity. We then conduct simulation studies to compare the relative performance of these two intervals with the best existing BCa bootstrap interval, proposed by Platt et al. Our simulation results show that the newly proposed intervals are better than the BCa bootstrap interval in terms of coverage accuracy and interval length.

Computer Simulation↗