The Laboratoire International Associé between the Centre National de la Recherche Scientifique and the University of Illinois at Urbana-Champaign was launched at the end of 2012. Its primary objective is to develop methods for high-performance molecular simulation with the aim of understanding the function of complex biological assemblies, transcending the frontiers of traditional disciplines by uniting mathematicians, physicists, theoretical chemists and biologists on both sides of the Atlantic. In France, the major contributors are located at the Université de Lorraine, the École des Ponts ParisTech, the Institut de Biologie Structurale and the Laboratoire de Biologie Physico-Chimique. In the United States, the contributors belong to the NIH Resource for Macromolecular Modeling and Bioinformatics. In Nancy, the partner is a theoretical chemistry and biophysics group incepted in 2003. Its expertise lies in describing the structure and the dynamic properties of the biological membrane and elucidating the mechanisms of the cell machinery. To attain this goal, its members leverage numerical simulations over size and timescales commensurate with the biological process at hand. Over the years, the team has gleaned milestone results in such diverse research areas as membrane transport, interaction with the biological membrane, membrane protein structure and function, as well as self-organized molecular systems. They also develop original approaches in the field of free-energy calculations to tackle rare events in biology.
Highlight
Accurate determination of protein:ligand standard binding free energies from molecular dynamics simulations. Designing a reliable computational methodology to calculate protein:ligand standard binding free energies is extremely challenging. The large change in configurational enthalpy and entropy that accompanies the association of ligand and protein is notoriously difficult to capture in naive brute-force simulations. Addressing this issue, the present protocol rests upon a rigorous statistical mechanical framework for the determination of protein:ligand binding affinities together with the comprehensive Binding Free-Energy Estimator 2 (BFEE2) application software. With the knowledge of the bound state, available from experiments or docking, application of the BFEE2 protocol with a reliable force field supplies in a matter of days standard binding free energies within chemical accuracy, for a broad range of protein:ligand complexes. Limiting undesirable human intervention, BFEE2 assists the end user in preparing all the necessary input files and performing the post-treatment of the simulations towards the final estimate of the binding affinity. Nature Protocols, 2022.
Recent publications
Free Energy Methods for the Description of Molecular Processes
Christophe Chipot;
Annual Review of Biophysics (2023) 52 (1):
A Practical Guide to Recent Advances in Multiscale Modeling and Simulation of BiomoleculesEnhanced Sampling Based on Collective Variables
Yong Wang; Ruhong Zhou; Haohao Fu; Wensheng Cai; Christophe Chipot; Xueguang Shao; (2023) 1-22
Chasing collective variables using temporal data-driven strategies
Haochuan Chen; Christophe Chipot;
QRB Discovery (2023) 413 (242-