دورية أكاديمية
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Parsing Dynamics of Protein Backbone NH and Side-Chain Methyl Groups using Molecular Dynamics Simulations.

التفاصيل البيبلوغرافية
العنوان: Parsing Dynamics of Protein Backbone NH and Side-Chain Methyl Groups using Molecular Dynamics Simulations.
المؤلفون: Banayan NE; Department of Biological Sciences, Columbia University, 3000 Broadway, New York, New York 10027, United States., Hsu A; Department of Chemistry, Columbia University, 3000 Broadway, New York, New York 10027, United States., Hunt JF; Department of Biological Sciences, Columbia University, 3000 Broadway, New York, New York 10027, United States., Palmer AG 3rd; Department of Biochemistry and Molecular Biophysics, Columbia University, 701 West 168th Street, New York, New York 10032, United States., Friesner RA; Department of Chemistry, Columbia University, 3000 Broadway, New York, New York 10027, United States.
المصدر: Journal of chemical theory and computation [J Chem Theory Comput] 2024 Jul 23; Vol. 20 (14), pp. 6316-6327. Date of Electronic Publication: 2024 Jul 03.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Chemical Society Country of Publication: United States NLM ID: 101232704 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1549-9626 (Electronic) Linking ISSN: 15499618 NLM ISO Abbreviation: J Chem Theory Comput Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Chemical Society, c2005-
مواضيع طبية MeSH: Molecular Dynamics Simulation* , Ribonuclease H*/chemistry , Ribonuclease H*/metabolism , Escherichia coli*/chemistry , Escherichia coli*/enzymology, Protein Conformation ; Nuclear Magnetic Resonance, Biomolecular
مستخلص: Experimental NMR spectroscopy and theoretical molecular dynamics (MD) simulations provide complementary insights into protein conformational dynamics and hence into biological function. The present work describes an extensive set of backbone NH and side-chain methyl group generalized order parameters for the Escherichia coli ribonuclease HI (RNH) enzyme derived from 2-μs microsecond MD simulations using the OPLS4 and AMBER-FF19SB force fields. The simulated generalized order parameters are compared with values derived from NMR 15 N and 13 CH 2 D spin relaxation measurements. The squares of the generalized order parameters, S 2 for the N-H bond vector and S axis 2 for the methyl group symmetry axis, characterize the equilibrium distribution of vector orientations in a molecular frame of reference. Optimal agreement between simulated and experimental results was obtained by averaging S 2 or S axis 2 calculated by dividing the simulated trajectories into 50 ns blocks (∼five times the rotational diffusion correlation time for RNH). With this procedure, the median absolute deviations (MAD) between experimental and simulated values of S 2 and S axis 2 are 0.030 (NH) and 0.061 (CH 3 ) for OPLS4 and 0.041 (NH) and 0.078 (CH 3 ) for AMBER-FF19SB. The MAD between OPLS4 and AMBER-FF19SB are 0.021 (NH) and 0.072 (CH 3 ). The generalized order parameters for the methyl group symmetry axis can be decomposed into contributions from backbone fluctuations, between-rotamer dihedral angle transitions, and within-rotamer dihedral angle fluctuations. Analysis of the simulation trajectories shows that ( i ) backbone and side chain conformational fluctuations exhibit little correlation and that ( ii ) fluctuations within rotamers are limited and highly uniform with values that depend on the number of dihedral angles considered. Low values of S axis 2 , indicative of enhanced side-chain flexibility, result from between-rotamer transitions that can be enhanced by increased local backbone flexibility.
المشرفين على المادة: EC 3.1.26.4 (Ribonuclease H)
EC 3.1.26.4 (ribonuclease HI)
تواريخ الأحداث: Date Created: 20240703 Date Completed: 20240723 Latest Revision: 20240723
رمز التحديث: 20240723
DOI: 10.1021/acs.jctc.4c00378
PMID: 38957960
قاعدة البيانات: MEDLINE
الوصف
تدمد:1549-9626
DOI:10.1021/acs.jctc.4c00378