Seminar Series

IDP Conversations

Date and Time

06 July 2022
11 AM (EDT) / 5 PM (CEST)

Session Link

The seminar series may be recorded and shared for later viewing.

Past Sessions

New Equilibrium presents IDP Conversations, a monthly seminar series focused on intrinsically disordered proteins (IDPs). Our goal is to foster a multi-perspective discussion on modeling and targeting IDPs. Each seminar, featuring speakers across academia and industry, includes a 40-minute presentation followed by a conversation.

Integrating NMR data (and more) with molecular simulations to determine protein structural ensembles

Understanding the molecular mechanisms used by biological systems to perform their functions is often essential to rationally target associated diseases. In many cases, the determination of the three-dimensional structure of these systems provides precious insights. However, it is often the interplay between structural and dynamical properties that determines the behavior of complex systems. While both experimental and computational methods are invaluable tools to study protein structure and dynamics, limitations in each individual technique can hamper their capabilities [1]. On one hand, determining structural models solely from experimental data is challenging as data often come from ensemble-averaged measurements over conformationally heterogeneous states, provide sparse and sometimes ambiguous information, and are subject to random and systematic errors. On the other hand, structural models determined by computational approaches such as molecular dynamics are limited by the inaccuracies of the force fields used as well as by the challenge of exhaustively sampling the conformational landscape of complex systems. Here I will present two combined computational-experimental approaches to integrate NMR data into molecular simulations to determine accurate protein structural ensembles of dynamic systems. I will illustrate these methods using two different applications. The first is the characterization of the structural ensembles of amyloid-β using NMR spectroscopy data and the study of the effect of a small molecule on this disordered system [2,3]. The second is the refinement of the structural ensembles of a set of disordered proteins, which were previously determined by microseconds-long MD simulations [4], by integration of a large variety of different experimental data. 

[1] M. Bonomi, G. T. Heller, C. Camilloni, M. Vendruscolo. Curr. Opin. Struct. Biol. 42 (2017) 106
[2] M. Bonomi, C. Camilloni, A. Cavalli, M. Vendruscolo. Sci. Adv. 2 (2016) e1501177
[3] G. T. Heller, et al. Sci. Adv. 6 (2020) eabb5924 
[4] P. Robustelli, S. Piana, D. E. Shaw. PNAS 115 (2018) E4758

Speaker: Massimiliano Bonomi, Ph.D.

Massimiliano Bonomi obtained his PhD in chemistry from ETH Zurich working with Prof. Michele Parrinello on the development and applications of enhanced-sampling algorithms for molecular dynamics simulations. His research was focused on the study of biological processes, such as the folding of peptides and small proteins, by means of advanced simulation techniques. During his postdocs at University of California (Sali group) and University of Cambridge (Vendruscolo group), he worked on the development and applications of methods based on Bayesian statistics to model structure and dynamics of proteins and macromolecular complexes by integrating noisy, ambiguous, and sparse experimental data collected on conformationally heterogeneous samples. In October 2018, he obtained a tenured position as CNRS researcher at Institut Pasteur (Paris, France), where he is currently group leader. His group is focused on the development of integrative computational/experimental approaches to characterize structure and dynamics of biological systems.

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