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 et Chimie des Protéines-Université Claude Bernard and the Laboratoire d'Ingénierie des Systèmes Macromoléculaires-Université d'Aix-Marseille. 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, as well as that of intermolecular potentials.
AlaScan: A graphical user interface for alanine scanning free-energy calculations. Computation of the free-energy changes that underlie molecular recognition and association has gained significant importance due to its considerable potential in drug discovery. The massive increase of computational power in recent years substantiates the application of more accurate theoretical methods for the calculation of binding free energies. The impact of such advances is the application of parent approaches, like computational alanine scanning, to investigate in silico the effect of aminoacid replacement in protein−ligand and protein−protein complexes, or probe the thermostability of individual proteins. Because human effort represents a significant cost that precludes the routine use of this form of free-energy calculations, minimizing manual intervention constitutes a stringent prerequisite for any such systematic computation. With this objective in mind, we propose a new plug-in, referred to as AlaScan, developed within the popular visualization program VMD to automate the major steps in alanine-scanning calculations, employing free-energy perturbation as implemented in the widely used molecular dynamics code NAMD. The AlaScan plug-in can be utilized upstream, to prepare input files for selected alanine mutations. It can also be utilized downstream to perform the analysis of different alanine-scanning calculations and to report the free-energy estimates in a user-friendly graphical user interface, allowing favorable mutations to be identified at a glance. The plug-in also assists the end-user in assessing the reliability of the calculation through rapid visual inspection. Journal of Chemical Information and Theory, 2016.
Correlation of bistranded clustered abasic DNA lesion processing with structural and dynamic DNA helix distortion.
Nucleic Acids Res.
2016, (44), 8588-8599.
Wang, S.; Zhao, T.; Shao, X.; Chipot, C.; Cai, W.
Complex movements in rotaxanes: Shuttling coupled with conformational transition of cyclodextrins
J. Phys. Chem. C
2016, (120), 19479-19486.
Gattuso, H.; Durand, E.; Bignon, E.; Morell, C.; Georgakilas, A. G.; Dumont, E.; Chipot, C.; Dehez, F.; Monari, A.
Repair rate of clustered abasic DNA lesions by human endonuclease: Molecular bases of sequence specificity
J. Phys. Chem. Lett
2016, (19), 3760-3765.