195,238 research outputs found
RosettaBackrub--a web server for flexible backbone protein structure modeling and design.
The RosettaBackrub server (http://kortemmelab.ucsf.edu/backrub) implements the Backrub method, derived from observations of alternative conformations in high-resolution protein crystal structures, for flexible backbone protein modeling. Backrub modeling is applied to three related applications using the Rosetta program for structure prediction and design: (I) modeling of structures of point mutations, (II) generating protein conformational ensembles and designing sequences consistent with these conformations and (III) predicting tolerated sequences at protein-protein interfaces. The three protocols have been validated on experimental data. Starting from a user-provided single input protein structure in PDB format, the server generates near-native conformational ensembles. The predicted conformations and sequences can be used for different applications, such as to guide mutagenesis experiments, for ensemble-docking approaches or to generate sequence libraries for protein design
Prediction of protein distance maps by assembling fragments according to physicochemical similarities
The prediction of protein structures is a current issue of great significance
in structural bioinformatics. More specifically, the prediction of the tertiary structure
of a protein consists of determining its three-dimensional conformation based
solely on its amino acid sequence. This study proposes a method in which protein
fragments are assembled according to their physicochemical similarities, using information
extracted from known protein structures. Many approaches cited in the
literature use the physicochemical properties of amino acids, generally hydrophobicity,
polarity and charge, to predict structure. In our method, implemented with
parallel multithreading, a set of 30 physicochemical amino acid properties selected
from the AAindex database were used. Several protein tertiary structure prediction
methods produce a contact map. Our proposed method produces a distance map,
which provides more information about the structure of a protein than a contact
map. The results of experiments with several non-homologous protein sets demonstrate
the generality of this method and its prediction quality using the amino acid
properties considered
A biophysical approach to large-scale protein-DNA binding data
About this book * Cutting-edge genome analysis methods from leading bioinformaticians An accurate description of current scientific developments in the field of bioinformatics and computational implementation is presented by research of the BioSapiens Network of Excellence. Bioinformatics is essential for annotating the structure and function of genes, proteins and the analysis of complete genomes and to molecular biology and biochemistry. Included is an overview of bioinformatics, the full spectrum of genome annotation approaches including; genome analysis and gene prediction, gene regulation analysis and expression, genome variation and QTL analysis, large scale protein annotation of function and structure, annotation and prediction of protein interactions, and the organization and annotation of molecular networks and biochemical pathways. Also covered is a technical framework to organize and represent genome data using the DAS technology and work in the annotation of two large genomic sets: HIV/HCV viral genomes and splicing alternatives potentially encoded in 1% of the human genome
Bivariate estimation of distribution algorithms for protein structure prediction.
A real-valued bivariate ‘Estimation of Distribution Algorithm’ specific for the ab initio and full-atom Protein Structure Prediction problem is proposed. It is known that this is a multidimensional and multimodal problem. In order to deal with the multimodality and the correlation of dihedral angles φ and ψ, we developed approaches based on Kernel Density Estimation and Finite Gaussian Mixtures. Simulation results have shown that both techniques are promising when applied to that problem
ProtNN: Fast and Accurate Nearest Neighbor Protein Function Prediction based on Graph Embedding in Structural and Topological Space
Studying the function of proteins is important for understanding the
molecular mechanisms of life. The number of publicly available protein
structures has increasingly become extremely large. Still, the determination of
the function of a protein structure remains a difficult, costly, and time
consuming task. The difficulties are often due to the essential role of spatial
and topological structures in the determination of protein functions in living
cells. In this paper, we propose ProtNN, a novel approach for protein function
prediction. Given an unannotated protein structure and a set of annotated
proteins, ProtNN finds the nearest neighbor annotated structures based on
protein-graph pairwise similarities. Given a query protein, ProtNN finds the
nearest neighbor reference proteins based on a graph representation model and a
pairwise similarity between vector embedding of both query and reference
protein-graphs in structural and topological spaces. ProtNN assigns to the
query protein the function with the highest number of votes across the set of k
nearest neighbor reference proteins, where k is a user-defined parameter.
Experimental evaluation demonstrates that ProtNN is able to accurately classify
several datasets in an extremely fast runtime compared to state-of-the-art
approaches. We further show that ProtNN is able to scale up to a whole PDB
dataset in a single-process mode with no parallelization, with a gain of
thousands order of magnitude of runtime compared to state-of-the-art
approaches
Predicting kinase inhibitor resistance: Physics-based and data-driven approaches.
Resistance to small molecule drugs often emerges in cancer cells, viruses, and bacteria as a result of the evolutionary pressure exerted by the therapy. Protein mutations that directly impair drug binding are frequently involved in resistance, and the ability to anticipate these mutations would be beneficial in drug development and clinical practice. Here, we evaluate the ability of three distinct computational methods to predict ligand binding affinity changes upon protein mutation for the cancer target Abl kinase. These structure-based approaches rely on first-principle statistical mechanics, mixed physics- and knowledge-based potentials, and machine learning, and were able to estimate binding affinity changes and identify resistant mutations with remarkable accuracy. We expect that these complementary approaches will enable the routine prediction of resistance-causing mutations in a variety of other target proteins
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