BioExcel Webinar #16 - NAFlex, a web server for the study of nucleic acid flexibility

Nucleic acid polymers are highly flexible entities, undergoing many conformational alterations and their structural polymorphic nature depends on the sequence and on external environmental conditions or the presence of ligands.

Experimental studies and data available in the Protein Data Bank (PDB) provide conformational information and illustrate the variety of the possible structures, but they are limited in providing information regarding flexibility. In order to explore the sequence-dependent flexibility of DNA and the effect of external factors, atomistic molecular dynamics (MD) simulations are widely used¹. As computer power increases and the reliability of force fields improve, more reliable information is derived from atomistic MD simulations. Such simulations have revealed the extent, and the complexity, of DNA movements and their tight coupling to the nature and dynamics of the environment. 

Here we present NAFlex², a web tool designed to facilitate the use of nucleic acid simulation tools for newcomers to the field. The server allows the user to study the flexibility of nucleic acids, either isolated or bound to other molecules. The server offers a variety of methods to explore nucleic acid flexibility, a base-pair resolution mesoscopic model and atomistic molecular dynamics simulations with a wide variety of protocols and force fields^3,4. The trajectories can be obtained by simulations, or imported externally⁵. In the latter case, NAFlex is directly connected with the MDWeb technology⁶. MDWeb allows the user to set up their own MD simulation, helps the user during all the setup and equilibration steps, providing all the input files required to launch the simulations. Finally, the trajectory obtained (and uploaded) can be visualized and analyzed directly in NAFlex server, using a large number of tools, including standard Cartesian analysis, essential dynamics, helical analysis, local and global stiffness, energy decomposition, principal components and in silico NMR spectra. The server is accessible free of charge from the mmb.irbbarcelona.org/NAFlex webpage, and is integrated in the Multiscale Complex Genomics Virtual Research Environment (MuG-VRE).