Characterizing protein motions from structure
Graphical abstract
.
Highlights
► Aggregate conformational ensembles provide a basis for quantitative comparisons. ► Geometric simulation using FRODA efficiently characterizes native state dynamics. ► Robust sampling is obtained in ANM and FRODA, but not using MD. ► Underlying structure plays the dominant role in determining essential dynamics.
Section snippets
Introduction:
The protein data bank [1], [2] (PDB) (www.pdb.org) is a repository of protein structures that continues to grow on a daily basis containing tens of thousands of structures derived from X-ray and nuclear diffraction and NMR. A key component of protein science is to generate an ensemble of conformations when provided a static structure in order to identify essential motions important to function. Molecular Dynamics (MD) [3] is a model that implements a force field to represent interactions of a
Anisotropic Network Model (ANM)
ANM calculations were done using the Anisotropic Network Model web server.
All runs were performed online at http://ignmtest.ccbb.pitt.edu/cgi-bin/anm/.
Each analysis used a distance cutoff of 15 Å and a weighted C–C distance of 2.5 Å.
Molecular dynamics (MD)
MD trajectories were downloaded [16] from www.Dynameomics.org.
The methodology used to generate the trajectories is available at the same URL.
Geometrical simulation (FIRST/FRODA)
FRODA trajectories were created using FIRST/FRODA version 6.2. Software downloaded [13] from http://flexweb.asu.edu/.
For each
The dynamical models and essential dynamics
FIRST uses a set of parameters that determine how constraints are identified, which is ultimately responsible for outcomes in determining the number of iDOF and the predicted rigid and flexible regions of a protein. Based on the RCD, a geometric simulation using FRODA is very efficient. The advantage of FIRST/FRODA is that the generation of output structures is by some comparisons four orders of magnitude faster than MD. However, this tremendous gain in speed comes at the price of
Conclusions
The existence for a range of physicality using FRODA has been demonstrated in this work for the first time. For the four proteins studied here: We established that the default settings for hydrophobic tethers (rule H3) combined with a H-bond energy cutoff between −1 kcal/mol to −3 kcal/mol is robust. For much larger proteins, the H-bond energy cutoff range may shift slightly lower because the decrease in surface to volume in larger proteins gives slightly higher density of H-bonds. More
Acknowledgements
We wish to thank Dan Farrell and Mike Thorpe for their support of the FRODA software, especially in regards to keeping us current with new features as they are added. This work has been supported in part by NIH (GM073082) and a subcontract from Pennsylvania State University through NIH (HL093531).
References (41)
- et al.
The Protein Data Bank: a computer-based archival file for macromolecular structures
J. Mol. Biol.
(1977) - et al.
Direct evaluation of thermal fluctuations in proteins using a single parameter harmonic potential
Folding Des.
(1997) - et al.
Anisotropy of fluctuation dynamics of proteins with an elastic network model
Biophys. J.
(2001) - et al.
SCOP: a structural classification of proteins database for the investigation of sequences and structures
J. Mol. Biol.
(1995) - et al.
Dynameomics: a comprehensive database of protein dynamics
Structure
(2010) - et al.
Collective protein dynamics in relation to function
Curr. Opin. Struct. Biol.
(2000) - et al.
Close Correspondence between the motions from principal component analysis of multiple HIV-1 protease structures and elastic network modes
Structure
(2008) - et al.
An analysis of core deformations in protein superfamilies
Biophys. J.
(2005) - et al.
On Principal Angles between Subspaces
Lin. Algeb. Appl.
(1992) - et al.
Crystal structures of myoglobin-ligand complexes at near-atomic resolution
Biophys. J.
(1999)
Structure and stability of an immunoglobulin superfamily domain from twitchin, a muscle protein of the nematode Caenorhabditis elegans
J. Mol. Biol.
Structure of ubiquitin refined at 1.8 A resolution
J. Mol. Biol.
A flexible approach for understanding protein stability
FEBS Lett.
Elucidating quantitative stability-flexibility relationships within thioredoxin and its fragments using a distance constraint model
J. Mol. Biol.
On the largest principal angle between random subspaces
Lin. Algeb. Appl.
Kinetics and thermodynamics of the rate-limiting conformational change in the actomyosin V mechanochemical cycle
J. Mol. Biol.
The protein data bank
Nucl. Acids Res.
Dynamics of folded proteins
Nature
Principal component analysis and long time protein dynamics
J. Phys. Chem.
Large amplitude elastic motions in proteins from a single-parameter, atomic analysis
Phys. Rev. Lett.
Cited by (21)
Dynamic rotation featured translocations of human serum albumin with a conical glass nanopore
2022, Journal of Electroanalytical ChemistryCitation Excerpt :In the natural state, proteins are in a tertiary structure and participate in life activities. Therefore, to study the mechanism of action of proteins in life activities, it is necessary to characterize or detect the structure of protein molecules to reveal the relationship between protein structure and function [1–6]. Due to the complexity and diversity of structures, higher requirements are placed on the characterization or detection of single-molecule proteins.
Constrained geometric simulation of the nicotinic acetylcholine receptor
2014, Journal of Molecular Graphics and ModellingCitation Excerpt :The principal component subspaces spanned by froda simulations have been shown to be very robust with respect to the chosen value of Ecut [22]. For froda dynamics, a step length of 0.1 Å [22] was employed. Sixteen simulations, each sampling 275,000 configurations, were run starting from the open-channel structure, and sixteen were run starting from the closed-channel structure.
Switch II mutants reveal coupling between the nucleotide- and actin-binding regions in myosin v
2012, Biophysical JournalCitation Excerpt :We generated all-atom trajectories using the Floppy Inclusion and Rigid Substructure Topology (FIRST)/Framework Rigidity Optimized Dynamic Algorithm (FRODA) software (35), version 6.2. The geometrical simulation paradigm (36,37) represents the molecular structure as a distance constraint network (36–38), which is used to explore accessible motions at the all-atom level of resolution. The FRODA simulations performed in this work mirror those of our previous study (22), with the exception of the starting structures.