Experiments and Simulations: A Pas de Deux to Unravel Biological Function

Understanding the molecular mechanisms underlying biological functions is essential to rationally target health and disease. This goal is often easier to achieve if an accurate characterization of the structural and dynamical properties of biological systems is available. While both experimental and computational methods provide invaluable tools, limitations in each of the individual techniques can hamper their predictive capabilities. Experimental data, which often come from time- and ensemble-averaged observations over conformationally heterogeneous states, provide sparse and sometimes ambiguous information, and are always subject to random and systematic errors. On the other hand, computational approaches such as molecular dynamics simulations are limited by the inaccuracies of the simplified physicochemical models and/or force field used to predict structural and dynamical properties, as well as by the difficulty to exhaustively sample the conformational landscape of complex systems. A combined and integrative use of experiments and simulations has been proven to be a successful strategy to study the behavior of biological systems.

The goal of this Research Topic is to explore the different avenues for using experimental and computational approaches in synergy in order to accurately characterize structure, dynamics, and ultimately function of biological systems. A wide spatial spectrum of systems will be covered: from ordered and disordered proteins, small molecules interacting with proteins, protein complexes, RNA, DNA, up to entire cells. Molecular simulations at various degrees of resolution and accuracy of the physico-chemical description of the system will be considered: ab-initio, quantum mechanics/molecular mechanics, classical - at both atomistic and coarse-grained levels. The integration of molecular simulations with different types of experimental data will be investigated, including X-ray crystallography, Cryo-electron microscopy and tomography, Nuclear Magnetic Resonance spectroscopy, biochemical measurements, Small Angle X-ray Scattering, and single-molecule Fluorescence Resonance Energy Transfer data.

Computational and experimental approaches to characterize protein structure and dynamics can be used in several different synergistic ways. This Research Topic will explore the following four areas:

• How to use simulations to assist the interpretation of experimental data
• How to use simulations to design and propose novel experiments
• How to use experimental data to validate molecular simulations
• A tighter integration: how to use experimental data to drive and/or refine molecular simulations.

This Research Topic is open to different types of contributions such as Original Research articles in the fields of both method development and applications, Reviews, Perspectives, and all other article types supported by the publisher (please find a full list including descriptions here)