MOTIVATION: A new algorithm to trace conformational transitions in proteins is presented. The method uses discrete molecular dynamics as engine to sample protein conformational space. A multiple minima Go-like potential energy function is used in combination with several enhancing sampling strategies, such as metadynamics, Maxwell Demon molecular dynamics and essential dynamics. The method, which shows an unprecedented computational efficiency, is able to trace a wide range of known experimental transitions. Contrary to simpler methods our strategy does not introduce distortions in the chemical structure of the protein and is able to reproduce well complex non-linear conformational transitions. The method, called GOdMD, can easily introduce additional restraints to the transition (presence of ligand, known intermediate, known maintained contacts, …) and is freely distributed to the community through the Spanish National Bioinformatics Institute (http://mmb.irbbarcelona.org/GOdMD). AVAILABILITY: Freely available on the web at http://mmb.irbbarcelona.org/GOdMD.

Abstract Summary: FlexServ is a web-based tool for the analysis of protein flexibility. The server incorporates powerful protocols for the coarse-grained determination of protein dynamics using different versions of Normal Mode Analysis (NMA), Brownian dynamics (BD) and Discrete Dynamics (DMD). It can also analyze user provided trajectories. The server allows a complete analysis of flexibility using a large variety of metrics, including basic geometrical analysis, B-factors, essential dynamics, stiffness analysis, collectivity measures, Lindemann's indexes, residue correlation, chain-correlations, dynamic domain determination, hinge point detections, etc. Data is presented through a web interface as plain text, 2D and 3D graphics. Availability: http://mmb.pcb.ub.es/FlexServ; http://www.inab.org Contact: [email protected] or [email protected] Supplementary information: Additional information and methodology details can be found at http://mmb.pcb.ub.es/FlexServ/help.