RT Journal Article SR Electronic T1 CryoFold: Ab-initio structure determination from electron density maps using molecular dynamics JF bioRxiv FD Cold Spring Harbor Laboratory SP 687087 DO 10.1101/687087 A1 Mrinal Shekhar A1 Genki Terashi A1 Chitrak Gupta A1 Gaspard Debussche A1 Nicholas J. Sisco A1 Jonathan Nguyen A1 James Zook A1 John Vant A1 Daipayan Sarkar A1 Petra Fromme A1 Wade D. Van Horn A1 Ken Dill A1 Daisuke Kihara A1 Emad Tajkhorshid A1 Alberto Perez A1 Abhishek Singharoy YR 2019 UL http://biorxiv.org/content/early/2019/07/02/687087.abstract AB Cryo-EM is a powerful method for determining biomolecular structures. But, unlike X-ray crystallography or solution-state NMR, which are data-rich, cryo-EM can be data-poor. Cryo-EM routinely gives electron density information to about 3–5 Å and the resolution often varies across the structure. So, it has been challenging to develop an automated computer algorithm that converts the experimental density maps to complete molecular structures. We address this challenge with CryoFold, a computational method that finds the chain trace from the density maps using MAINMAST, then performs molecular dynamics simulations using ReMDFF, a resolution-exchange flexible fitting protocol, accelerated by MELD, which uses low-information data to broaden the relevant conformational searching of secondary and tertiary structures. We describe four successes of structure determinations, including for membrane proteins and large molecules. CryoFold handles input data that is heterogeneous, and even sparse. The software is automated, and is available to the public via a python-based graphical user interface.