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Here we present a program aimed at free-energy calculations in molecular systems. It consists of a series of routines that can be interfaced with the most popular classical molecular dynamics (MD) codes through a simple patching procedure. This leaves the possibility for the user to exploit many different MD engines depending on the system simulated and on(More)
Enhancing sampling and analyzing simulations are central issues in molecular simulation. Recently, we introduced PLUMED, an open-source plug-in that provides some of the most popular molecular dynamics (MD) codes with implementations of a variety of different enhanced sampling algorithms and collective variables (CVs). The rapid changes in this field, in(More)
The authors present a new method for searching low free energy paths in complex molecular systems at finite temperature. They introduce two variables that are able to describe the position of a point in configurational space relative to a preassigned path. With the help of these two variables the authors combine features of approaches such as metadynamics(More)
Topotecan (TPT) is a topoisomerase I inhibitor, and like the other drugs of this family, it is believed to act in a specific way on cells in S phase at the time of treatment. Exploiting a new method, coupling a particular experimental plan with computer simulation, a complete quantitative study of the time dependence and dose dependence of the activity of(More)
The translocation of ions and water across cell membranes is a prerequisite for many of life's processes. K(+) channels are a diverse family of integral membrane proteins through which K(+) can pass selectively. There is an ongoing debate about the nature of conformational changes associated with the opening and closing and conductive and nonconductive(More)
Metadynamics is an established sampling method aimed at reconstructing the free-energy surface relative to a set of appropriately chosen collective variables. In standard metadynamics, the free-energy surface is filled by the addition of Gaussian potentials of preassigned and typically diagonal covariance. Asymptotically the free-energy surface is(More)
We study the ligand (tetramethylammonium) recognition by the peripheral anionic site and its penetration of the human AChE gorge by using atomistic molecular dynamics simulations and our recently developed metadynamics method. The role of both the peripheral anionic site and the formation of cation-pi interactions in the ligand entrance are clearly shown.(More)
We used density functional theory to investigate the capacity for carbon monoxide (CO) release of five newly synthesized manganese-containing CO-releasing molecules (CO-RMs), namely CORM-368 (1), CORM-401 (2), CORM-371 (3), CORM-409 (4), and CORM-313 (5). The results correctly discriminated good CO releasers (1 and 2) from a compound unable to release CO(More)
Kinase large-scale conformational rearrangement is an issue of enormous biological and pharmacological relevance. Atomistic simulations able to capture the dynamics and the energetics of kinase large-scale motions are still in their infancy. Here, we present a computational study in which the atomistic dynamics of the "open-to-closed" movement of the(More)
The influence of the state of the bound nucleotide (ATP, ADP-Pi, or ADP) on the conformational free-energy landscape of actin is investigated. Nucleotide-dependent folding of the DNase-I binding (DB) loop in monomeric actin and the actin trimer is carried out using all-atom molecular dynamics (MD) calculations accelerated with a multiscale implementation of(More)