Tuyển tập các báo cáo nghiên cứu về sinh học được đăng trên tạp chí y học Molecular Biology cung cấp cho các bạn kiến thức về ngành sinh học đề tài: Sparse estimation for structural variability. | Hosur et al. Algorithms for Molecular Biology 2011 6 12 http content 6 1 12 AMR ALGORITHMS FOR MOLECULAR BIOLOGY RESEARCH Open Access Sparse estimation for structural variability Raghavendra Hosur1 3 Rohit Singh1 and Bonnie Berger1 2 Abstract Background Proteins are dynamic molecules that exhibit a wide range of motions often these conformational changes are important for protein function. Determining biologically relevant conformational changes or true variability efficiently is challenging due to the noise present in structure data. Results In this paper we present a novel approach to elucidate conformational variability in structures solved using X-ray crystallography. We first infer an ensemble to represent the experimental data and then formulate the identification of truly variable members of the ensemble as opposed to those that vary only due to noise as a sparse estimation problem. Our results indicate that the algorithm is able to accurately distinguish genuine conformational changes from variability due to noise. We validate our predictions for structures in the Protein Data Bank by comparing with NMR experiments as well as on synthetic data. In addition to improved performance over existing methods the algorithm is robust to the levels of noise present in real data. In the case of Human Ubiquitin-conjugating enzyme Ubc9 variability identified by the algorithm corresponds to functionally important residues implicated by mutagenesis experiments. Our algorithm is also general enough to be integrated into state-of-the-art software tools for structure-inference. Introduction A central tenet of molecular biology is that a protein s three-dimensional 3D structure is crucial to its function. Indeed the structural genomics initiative is producing an ever increasing number of structures at high resolution providing accurate coordinates for each atom in the structure 1 . A protein s structure however is rarely static. Proteins are dynamic molecules .
