Celebrating Benoît Roux's 60th birthday: quantifying biology at the membrane

We are pleased to dedicate this special issue of the Journal of Computational Chemistry, entitled “Membrane Protein Simulations and Free Energy Approaches”, to Professor Benoît Roux to mark the occasion of his 60th birthday. This issue is a collection of peer-reviewed articles contributed by 20 participants of a three-day symposium held for his 60th birthday celebration in August 2018 at the ACS 256th National Meeting in Boston, MA (Figure 1). This symposium was organized by three former Roux lab members (Wonpil Im, Nilesh Banavali, and Yun Lyna Luo) and brought together 46 of Benoît's friends, colleagues, and alumni. Benoît's seminal impact on the field of computational biophysics includes major innovations in quantitative free energy approaches to study molecular systems, which enabled deep advances in the understanding of membrane and protein dynamics and function. These inventive techniques have been also been applied to other challenging biological areas, such as macromolecular machines and protein-ligand binding. The articles selected in this special issue honor his pioneering research by showcasing the latest advances in biomolecular simulation, which demonstrate the vitality and variety of a computational biophysics community that Benoît has been instrumental in creating and fostering. Benoît and co-workers have been strongly involved in the development of two popular biomolecular modeling and molecular dynamics (MD) simulation software packages: CHARMM, dating back to his doctoral research with Professor Martin Karplus, and NAMD, through more recent collaborations with Professor Klaus Schulten. Novel method development has always been at the heart of Benoît's research program, and this is reflected in the research directions that his alumni have taken. In this issue, the Toby Allen group reviews the recent application of an atomistic string method, based on Benoît's “swarms-of-trajectories” approach, to elucidate the interdependence of conformational changes during pentameric ligand-gated ion channel activation. The Wonpil Im group presents a new tool in CHARMM-GUI that consists of two modules, Spin-Pair Distributor and restrained-ensemble MD Prepper, to setup simulations that utilize information from the powerful double electron–electron resonance (DEER) experiments. The Jose Faraldo-Gomez group presents a method to calculate the free energy of a shape transformation in a lipid membrane directly from enhanced sampling MD simulation using grid-based collective variable. The Yun Luo group reports a currentflow betweenness method for robust protein dynamical network analysis and revealed common changes in protein–protein networks among gain-of-function kinase mutants. Binding free energy calculations are an important objective in computational chemistry and drug design. Benoît is a trailblazer in absolute binding free energy calculations using both the alchemical double decoupling method and potential of mean force method. The David Minh group examines the impact of harmonic restraints on protein heavy atoms and ligand atoms on end-point free energy calculations. The Haibo Yu group uses implicit ligand sampling simulations to identify potential O2 binding site and migration pathways within a photoprotein obelin, which provides the basis for future computational studies of the bioluminescent mechanism. The Christopher Rowley group assesses several semi-empirical and density-functional theory (DFT) methods for their ability to describe the potential energy surface and reaction energies of the covalent modification of a thiol by an electrophile. The first polarizable model of water based on the classical Drude oscillator approach was developed by Guillaume Lamoureux, Alexander MacKerell Jr., and Benoît in 2003. Thanks to the continued efforts of Benoît and Alex, the Drude force field is now becoming the method of choice to account for induced polarization in large-scale biomolecular simulations. Two independent studies aimed at improving ion–π interactions are reported in this issue. The Guillaume Lamoureux group calibrates the Drude force field for complexes of alkali metal ions and ammoniums with aromatic model compounds. The Alexander MacKerell Jr. group systematically optimizes the parameters for anion-π interactions in proteins in the Drude-2013 protein polarizable force field. Lipid membranes serves as a physical barrier, substrate, and a mechanistically responsive environment in a wide range of physiological and pathological processes. The Christopher Chipot group calculates the free-energy and fractional-diffusivity profiles underlying membrane translocation and reveals that CO2 expands and loosens the membrane, which facilitates the permeation of the drug-like molecules. The Harel Weinstein group compares the responses of the membrane to the TMEM16 scramblases in flat membranes and nanodiscs. Using highly mobile membrane model and full membrane simulations, the Emad Tajkhorshid group reports the first observation of two distinct PIP3 binding modes on GRP1-PHD, demonstrate that concurrent binding of multiple anionic lipids by GRP1-PHD contributes to its membrane affinity. To understand the mechanism of cholesterol modification of hedgehog ligand, Nilesh Banavali models a cholesterol-bound drosophila Hh precursor and predicts atomic-detail pathways for the full autocatalytic reaction. The Yinglong Miao group DOI: 10.1002/jcc.26140