AbstractMotivation: 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.Contact: pablo@chaconlab.orgSupplementary Information: Supplementary data are available at Bioinformatics online.