Alessandro Laio

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We introduce a powerful method for exploring the properties of the multidimensional free energy surfaces (FESs) of complex many-body systems by means of coarse-grained non-Markovian dynamics in the space defined by a few collective coordinates. A characteristic feature of these dynamics is the presence of a history-dependent potential term that, in time,(More)
By suitably extending a recent approach [Bussi, G.; et al. J. Am. Chem. Soc. 2006, 128, 13435] we introduce a powerful methodology that allows the parallel reconstruction of the free energy of a system in a virtually unlimited number of variables. Multiple metadynamics simulations of the same system at the same temperature are performed, biasing each(More)
By suitably adapting a recent approach [A. Laio and M. Parrinello, Proc. Natl. Acad. Sci. U.S.A. 99, 12 562 (2002)]] we develop a powerful molecular dynamics method for the study of pressure-induced structural transformations. We use the edges of the simulation cell as collective variables and define a metadynamics that drives the system away from the local(More)
The possibility of observing chemical reactions in ab initio molecular dynamics runs is severely hindered by the short simulation time accessible. We propose a new method for accelerating the reaction process, based on the ideas of the extended Lagrangian and coarse-grained non-Markovian metadynamics. We demonstrate that by this method it is possible to(More)
In this Letter we propose a new formalism to map history-dependent metadynamics in a Markovian process. We apply this formalism to model Langevin dynamics and determine the equilibrium distribution of a collection of simulations. We demonstrate that the reconstructed free energy is an unbiased estimate of the underlying free energy and analytically derive(More)
It is currently believed that the atlas of existing protein structures is faithfully represented in the Protein Data Bank. However, whether this atlas covers the full universe of all possible protein structures is still a highly debated issue. By using a sophisticated numerical approach, we performed an exhaustive exploration of the conformational space of(More)
Trp-cage is a designed 20-residue polypeptide that, in spite of its size, shares several features with larger globular proteins.Although the system has been intensively investigated experimentally and theoretically, its folding mechanism is not yet fully understood. Indeed, some experiments suggest a two-state behavior, while others point to the presence of(More)
The post-perovskite phase of (Mg,Fe)SiO3 is believed to be the main mineral phase of the Earth's lowermost mantle (the D'' layer). Its properties explain numerous geophysical observations associated with this layer-for example, the D'' discontinuity, its topography and seismic anisotropy within the layer. Here we use a novel simulation technique,(More)
We develop a new free-energy method, based on the combination of parallel tempering and metadynamics, and apply this method to the calculation of the free-energy landscape of the folding beta hairpin in explicit water. We show that the combined method greatly improves the performance of both parallel tempering and metadynamics. In particular, we are able to(More)
Metadynamics is a powerful technique that has been successfully exploited to explore the multidimensional free energy surface of complex polyatomic systems and predict transition mechanisms in very different fields, ranging from chemistry and solid-state physics to biophysics. We here derive an explicit expression for the accuracy of the methodology and(More)