Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Sunday Speaker Abstracts

Integrative Structural and Dynamical Biology with PLUMED-ISDB Massimiliano Bonomi 1 , Carlo Camilloni 2 , Michele Vendruscolo 1 . 1 University of Cambridge, Cambridge, United Kingdom, 2 Technische Universität München, Garching, Germany. Accurate structural models of biological systems can be obtained by properly combining multiple sources of information, such as experimental data and a priori physico-chemical knowledge [1]. Here we present PLUMED-ISDB, an open-source, freely-available module of the popular PLUMED library [www.plumed.org; 2], which enables the simultaneous determination of structure and dynamics of conformationally heterogeneous systems by integrating experimental data with a priori information. This integration is achieved using metainference [3], a general Bayesian framework that accounts for both noise in the data and their ensemble averaged nature. PLUMED-ISDB implements different types of experimental data, such as several NMR observables, FRET, SAXS and cryo-electron microscopy data [4], and enables modelling structure and dynamics of individual proteins, protein complexes, membrane proteins, RNA, and DNA, using a variety of enhanced sampling methods and resolutions of the system. [1] M. Bonomi, G. T. Heller, C. Camilloni, M. Vendruscolo, Principles of protein structural ensemble determination. Curr. Opin. Struct. Biol. 42, 106-116 (2017). [2] G. A. Tribello, M. Bonomi, D. Branduardi, C. Camilloni, G. Bussi, PLUMED 2: New feathers for an old bird. Comp. Phys. Comm. 185, 604-613 (2014). [3] M. Bonomi, C. Camilloni, A. Cavalli, M. Vendruscolo, Metainference: A Bayesian inference method for heterogeneous systems. Sci. Adv. 2, e1501177 (2016). [4] S. Hanot et al., Multi-scale Bayesian modelling of cryo-electron microscopy density maps. bioRxiv doi: 10.1101/113951 (2017).

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