Group: Structural Biology Group TorVergata - with tag umbrella-sampling [4 articles]

Abstract

A practical approach that enables one to calculate the standard free energy of binding from a one-dimensional potential of mean force (PMF) is proposed. Umbrella sampling and the weighted histogram analysis method are used to generate a PMF along the reaction coordinate of binding. At each point, a restraint is applied orthogonal to the reaction coordinate to make possible the determination of the volume sampled by the ligand. The free energy of binding from an arbitrary unbound volume to the restrained ...

Abstract

The recently formulated weighted histogram analysis method (WHAM)1 is an extension of Ferrenberg and Swendsen's multiple histogram technique for free-energy and potential of mean force calculations. As an illustration of the method, we have calculated the two-dimensional potential of mean force surface of the dihedrals gamma and chi in deoxyadenosine with Monte Carlo simulations using the all-atom and united-atom representation of the AMBER force fields. This also demonstrates one of the major advantages of WHAM over umbrella sampling techniques. The method ...

Abstract

Topoisomerase I (top1) is the sole chemotherapeutic target for the anticancer alkaloid camptothecin and its analogs (CPTs). The CPTs mediate cytotoxicity by binding reversibly to transient top1−DNA covalent complexes. There is significant variation in the persistence of the resultant CPTs−top1−DNA ternary complexes formed. Presently, there is no reliable method that can be used to predict the persistence of the ternary complexes, significantly limiting formulation of structure−activity relationships. Here, we used molecular dynamics simulations to probe the properties of several CPTs that ...