Laboratory for Molecular Modelling and Dynamics

A protein is not a static structure. Its function emerges from motion: from the conformational changes that open and close binding sites, from competition between ligands, from the interaction with the membrane that anchors it. Simulating that motion at atomic resolution makes it possible to formulate testable hypotheses about mechanisms of action, and about how to interfere with them.

The relevant motion does not happen on a single scale. Bond vibrations and side-chain rotations take femtoseconds to picoseconds; the closing of a loop over an active site, nanoseconds; the transition between conformational states of a whole domain can take microseconds or longer. Each question calls for a method with the matching reach, which is why the laboratory combines classical molecular dynamics, elastic-network normal mode analysis and a quantum description of the reactive region, rather than treating every case with the same tool.

The practical consequence for drug design is that a crystal structure, or a static model, is a portrait and not the film. A binding site may exist in only part of the conformations a protein visits, and an apparently closed cavity may open through thermal fluctuation. Taking motion into account changes what counts as a tractable target, and changes which molecules are expected to bind to it.

The laboratory investigates therapeutic targets for diseases caused by HIV, DENV, ZIKV, Yersinia pestis and Trypanosoma cruzi, combining structural modelling, simulation and computational screening in collaboration with experimental groups.

The LMDM takes part in graduate programmes at UFRJ and hosts undergraduate, master’s, doctoral and postdoctoral researchers. Training ranges from the foundations of statistical mechanics and force fields to the operation of high-performance computing resources and the development of scientific software.