MOLECULAR DYNAMICS FLEXIBLE FITTING (MDFF)

University Of Illinois At Urbana-Champaign, Urbana IL

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cryo-electron microscopy provides density maps of biomolecular complexes in their functional states, but only at low resolution, unlike X-ray crystallography, which provides atomic-resolution structures of biomolecules but usually not in a physiological state. Computational methods to combine information from both techniques hold the promise of generating physiologically accurate, high-resolution structures of biomolecular complexes. To combine experimental data from these two sources, the Resource developed a novel method, molecular dynamics flexible fitting (MDFF; http://www.ks.uiuc.edu/Research/mdff) [1,2], to fit atomic structures into cryo-EM density maps. MDFF employs molecular dynamics (MD) to perform the fitting, which allows flexibility while maintaining a realistic conformation. The standard MD force field is modified by incorporating the EM density map as an attractive potential that drives atoms into high-density regions. Furthermore, restraints are applied to preserve secondary structure of the biomolecules. MDFF setup and analysis are performed with the Resource's molecular visualization program, VMD, and MDFF simulations are conducted using the Resource's MD simulation software, NAMD. Since NAMD is highly scalable and supports simulation of large systems, MDFF can be applied to large macromolecular complexes such as the ribosome [3].