Molecular Dynamics Flexible Fitting: All You Want to Know About Resolution Exchange

John W. Vant, Daipayan Sarkar, Chitrak Gupta, Mrinal S. Shekhar, Sumit Mittal, Abhishek Singharoy

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

1 Scopus citations

Abstract

In recent years, owing to the advances in instrumentation, cryo-EM has emerged as the go-to tool for obtaining high-resolution structures of biomolecular systems. However, building three-dimensional atomic structures of biomolecules from these high-resolution maps remains a concern for the traditional map-guided structure-determination schemes. Recently, we developed a computational tool, Resolution Exchange Molecular Dynamics Flexible Fitting (ReMDFF) to address this problem by re-refining a search model against a series of maps of progressively higher resolutions, which ends with the original experimental resolution (Wang et al., J Struct Biol 204(2):319–328, 2018). In this chapter, we present a step-by-step outline for preparing, executing, and analyzing ReMDFF refinements of simple proteins and multimeric complexes. The structure determination of carbon monoxide dehydrogenase and Mg2+-channel CorA are employed as case studies. All scripts are provided via GitHub (Vant, Resolution exchange molecular dynamics flexible fitting (ReMDFF) all you want to know about flexible fitting, 2019, https://github.com/jvant/ReMDFF_Singharoy_Group.git).

Original languageEnglish
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages301-315
Number of pages15
DOIs
StatePublished - 2020
Externally publishedYes

Publication series

NameMethods in Molecular Biology
Volume2165
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Funding

The authors acknowledge start-up funds from the School of Molecular Sciences and Center for Applied Structure Discovery at Arizona State University, and the resources of the OLCF at the Oak Ridge National Laboratory, which is supported by the Office of Science at DOE under Contract No. DE-AC05-00OR22725, made available via the INCITE program. We also acknowledge NAMD and VMD developments supported by NIH (P41GM104601) and R01GM098243-02 for supporting our study of membrane proteins.

FundersFunder number
School of Molecular Sciences and Center for Applied Structure Discovery at Arizona State University
National Institutes of HealthR01GM098243-02
U.S. Department of EnergyDE-AC05-00OR22725
National Institute of General Medical SciencesP41GM104601
Office of Science

    Keywords

    • Hybrid structure determination
    • Molecular dynamics flexible fitting
    • NAMD
    • Real-space refinement
    • Resolution exchange
    • VMD

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