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Anteghini, M.

Publications and source records attributed to Anteghini, M..

2 recordsLinked to original sources

In-Pero: Exploiting deep learning embeddings of protein sequences to predict the localisation of peroxisomal proteins

Peroxisomes are ubiquitous membrane-bound organelles, and aberrant localisation of peroxisomal proteins contributes to the pathogenesis of several disorders. Many computational methods focus on assigning protein sequences to subcellular compartments, but there are no specific tools tailored for the sub-localisation (matrix vs membrane) of peroxisome proteins. We present here In-Pero, a new method for predicting protein sub-peroxisomal cellular localisation. In-Pero combines standard machine learning approaches with recently proposed multi-dimensional deep-learning representations of the protein amino-acid sequence. It showed a classification accuracy above 0.9 in predicting peroxisomal matrix and membrane proteins. The method is trained and tested using a double cross-validation approach on a curated data set comprising 160 peroxisomal proteins with experimental evidence for sub-peroxisomal localisation. We further show that the proposed approach can be easily adapted (In-Mito) to the prediction of mitochondrial protein localisation obtaining performances for certain classes of proteins (matrix and inner-membrane) superior to existing tools. All data sets and codes are available at https://github.com/MarcoAnteghini and at www.systemsbiology.nl

bioinformatics

Thermodynamics and kinetics of the amyloid-β peptide revealed by Markov state models based on MD data in agreement with experiment

The amlyoid-{beta} peptide (A{beta}) is closely linked to the development of Alzheimers disease. Molecular dynamics (MD) simulations have become an indispensable tool for studying the behavior of this peptide at the (sub)molecular level, thereby providing insight into the molecular basis of Alzheimers disease. General key aspects of MD simulations are the force field used for modeling the peptide or protein and its environment, which is important for accurate modeling of the system of interest, and the length of the simulations, which determines whether or not equilibrium is reached. In this study we address these points by analyzing 30-{micro}s MD simulations acquired for A{beta}40 using seven different force fields. We assess the convergence of these simulations based on the convergence of various structural properties and of NMR and fluorescence spectroscopic observables. Moreover, we calculate Markov state models for each of the seven MD simulations, which provide an unprecedented view of the thermodynamics and kinetics of the amyloid-{beta} peptide. This further allows us to provide answers for pertinent questions, like: Which force fields are suitable for modeling A{beta}? (a99SB-UCB and a99SB-ILDN/TIP4P-D); What does A{beta} peptide really look like? (mostly extended and disordered) and; How long does it take MD simulations of A{beta} to attain equilibrium? (20-30 {micro}s). We believe the analyses presented in this study will provide a useful reference guide for important questions relating to the structure and dynamics of A{beta}in particular, and by extension other similar disordered peptides.

biophysics