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8 pags, 2 figs, 4 tabs. -- Supplementary data are available at Bioinformatics online., Motivation: Dynamic simulations of systems with biologically relevant sizes and time scales are critical for understanding macromolecular functioning. Coarse-grained representations combined with normal mode analysis (NMA) have been established as an alternative to atomistic simulations. The versatility and efficiency of current approaches normally based on Cartesian coordinates can be greatly enhanced with internal coordinates (IC). Results: Here, we present a new versatile tool chest to explore conformational flexibility of both protein and nucleic acid structures using NMA in IC. Consideration of dihedral angles as variables reduces the computational cost and non-physical distortions of classical Cartesian NMA methods. Our proposed framework operates at different coarse-grained levels and offers an efficient framework to conduct NMA-based conformational studies, including standard vibrational analysis, Monte-Carlo simulations or pathway exploration. Examples of these approaches are shown to demonstrate its applicability, robustness and efficiency. © The Author 2011. Published by Oxford University Press. All rights reserved., MICNN BFU2009-09552; Human Frontier Science Program RGP0039/2008

Motivation: Prediction of protein–protein complexes from the coordinates of their unbound components usually starts by generating many potential predictions from a rigid-body 6D search followed by a second stage that aims to refine such predictions. Here, we present and evaluate a new method to effectively address the complexity and sampling requirements of the initial exhaustive search. In this approach we combine the projection of the interaction terms into 3D grid-based potentials with the efficiency of spherical harmonics approximations to accelerate the search. The binding energy upon complex formation is approximated as a correlation function composed of van der Waals, electrostatics and desolvation potential terms. The interaction-energy minima are identified by a novel, fast and exhaustive rotational docking search combined with a simple translational scanning. Results obtained on standard protein–protein benchmarks demonstrate its general applicability and robustness. The accuracy is comparable to that of existing state-of-the-art initial exhaustive rigid-body docking tools, but achieving superior efficiency. Moreover, a parallel version of the method performs the docking search in just a few minutes, opening new application opportunities in the current ‘omics’ world. Availability: http://sbg.cib.csic.es/Software/FRODOCK/ Contact: Pablo@cib.csic.es Supplementary information: Supplementary data are available at Bioinformatics online.