Advances in the REDCAT software package

BMC Bioinformatics

Chris Schmidt¹  Stephanie J Irausquin¹  Homayoun Valafar¹ 

[1] Department of Computer Science & Engineering, University of South Carolina, Columbia, SC 29208, USA

关键词: RDC;    Xplor-NIH;    VMD;    Coupling;    Dipolar;    Residual;    Structure;    Protein;   

Others  :  1087734
DOI  :  10.1186/1471-2105-14-302

 received in 2013-04-30, accepted in 2013-09-13,  发布年份 2013

【 摘 要 】

Background

Residual Dipolar Couplings (RDCs) have emerged in the past two decades as an informative source of experimental restraints for the study of structure and dynamics of biological macromolecules and complexes. The REDCAT software package was previously introduced for the analysis of molecular structures using RDC data. Here we report additional features that have been included in this software package in order to expand the scope of its analyses. We first discuss the features that enhance REDCATs user-friendly nature, such as the integration of a number of analyses into one single operation and enabling convenient examination of a structural ensemble in order to identify the most suitable structure. We then describe the new features which expand the scope of RDC analyses, performing exercises that utilize both synthetic and experimental data to illustrate and evaluate different features with regard to structure refinement and structure validation.

Results

We establish the seamless interaction that takes place between REDCAT, VMD, and Xplor-NIH in demonstrations that utilize our newly developed REDCAT-VMD and XplorGUI interfaces. These modules enable visualization of RDC analysis results on the molecular structure displayed in VMD and refinement of structures with Xplor-NIH, respectively. We also highlight REDCAT’s Error-Analysis feature in reporting the localized fitness of a structure to RDC data, which provides a more effective means of recognizing local structural anomalies. This allows for structurally sound regions of a molecule to be identified, and for any refinement efforts to be focused solely on locally distorted regions.

Conclusions

The newly engineered REDCAT software package, which is available for download via the WWW from http://ifestos.cse.sc.edu webcite, has been developed in the Object Oriented C++ environment. Our most recent enhancements to REDCAT serve to provide a more complete RDC analysis suite, while also accommodating a more user-friendly experience, and will be of great interest to the community of researchers and developers since it hides the complications of software development.

【 授权许可】

   
2013 Schmidt et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

Figure 9.

Figure 10.

Figure 11.

Figure 12.

Figure 13.

Figure 14.

Figure 15.

Figure 16.

【 参考文献 】

• [1]Salmon L, Bouvignies G, Markwick P, Blackledge M: Nuclear magnetic resonance provides a quantitative description of protein conformational flexibility on physiologically important time scales. Biochemistry 2011, 50:2735-2747.
• [2]Bouvignies G, Bernadó P, Meier S, Cho K, Grzesiek S, Brüschweiler R, Blackledge M: Identification of slow correlated motions in proteins using residual dipolar and hydrogen-bond scalar couplings. Proc Natl Acad Sci USA 2005, 102:13885-13890.
• [3]Clore GM, Schwieters CD: Amplitudes of protein backbone dynamics and correlated motions in a small alpha/beta protein: correspondence of dipolar coupling and heteronuclear relaxation measurements. Biochemistry 2004, 43:10678-10691.
• [4]Tolman JR, Flanagan JM, Kennedy MA, Prestegard JH: NMR evidence for slow collective motions in cyanometmyoglobin. Nat Struct Biol 1997, 4:292-297.
• [5]Tolman JR, Ruan K: NMR residual dipolar couplings as probes of biomolecular dynamics. Chemical reviews 2006, 106:1720-1736.
• [6]Azurmendi HF, Martin-Pastor M, Bush CA: Conformational studies of Lewis X and Lewis A trisaccharides using NMR residual dipolar couplings. Biopolymers 2002, 63:89-98.
• [7]Azurmendi HF, Bush CA: Conformational studies of blood group A and blood group B oligosaccharides using NMR residual dipolar couplings. Carbohydr Res 2002, 337:905-915.
• [8]Adeyeye J, Azurmendi HF, Stroop CJM, Sozhamannan S, Williams AL, Adetumbi AM, Johnson JA, Bush CA: Conformation of the hexasaccharide repeating subunit from the Vibrio cholerae O139 capsular polysaccharide. Biochemistry 2003, 42:3979-3988.
• [9]Tian F, Al-Hashimi HM, Craighead JL, Prestegard JH: Conformational analysis of a flexible oligosaccharide using residual dipolar couplings. J Am Chem Soc 2001, 123:485-492.
• [10]Canales A, Jiménez-Barbero J, Martín-Pastor M: Review: use of residual dipolar couplings to determine the structure of carbohydrates. Magnetic resonance in chemistry: MRC 2012, 50(Suppl 1):S80-S85.
• [11]Al-Hashimi HM, Bolon PJ, Prestegard JH: Molecular symmetry as an aid to geometry determination in ligand protein complexes. J Magn Reson 2000, 142:153-158.
• [12]Al-Hashimi HM, Gosser Y, Gorin A, Hu W, Majumdar A, Patel DJ: Concerted motions in HIV-1 TAR RNA may allow access to bound state conformations: RNA dynamics from NMR residual dipolar couplings. Journal of molecular biology 2002, 315:95-102.
• [13]Al-Hashimi HM, Gorin A, Majumdar A, Gosser Y, Patel DJ: Towards structural Genomics of RNA: rapid NMR resonance assignment and simultaneous RNA tertiary structure determination using residual dipolar couplings. J Mol Biol 2002, 318:637-649.
• [14]Tjandra N, Tate S, Ono A, Kainosho M, Bax A: The NMR structure of a DNA dodecamer in an aqueous dilute liquid crystalline phase. J Am Chem Soc 2000, 122:6190-6200.
• [15]Vermeulen A, Zhou H, Pardi A: Determining DNA global structure and DNA bending by application of NMR residual dipolar couplings. J Am Chem Soc 2000, 122:9638-9647.
• [16]Getz M, Sun X, Casiano-negroni A, Zhang Q, Al-hashimi HM: Rna dynamics and conformational adaptation. Biopolymers 2007, 86:384-402.
• [17]Bertini I, Luchinat C, Turano P, Battaini G, Casella L: The magnetic properties of myoglobin as studied by NMR spectroscopy. Chemistry-a European Journal 2003, 9:2316-2322.
• [18]Andrec M, Du PC, Levy RM: Protein backbone structure determination using only residual dipolar couplings from one ordering medium. J biomol NMR 2001, 21:335-347.
• [19]Cornilescu G, Delaglio F, Bax A: Protein backbone angle restraints from searching a database for chemical shift and sequence homology. J Biomol NMR 1999, 13:289-302.
• [20]Fowler CA, Tian F, Al-Hashimi HM, Prestegard JH: Rapid determination of protein folds using residual dipolar couplings. J Mol Biol 2000, 304:447-460.
• [21]Clore GM, Bewley CA: Using conjoined rigid body/torsion angle simulated annealing to determine the relative orientation of covalently linked protein domains from dipolar couplings. J Magn Reson 2002, 154:329-335.
• [22]Assfalg M, Bertini I, Turano P, Grant Mauk A, Winkler JR, Gray HB: 15N-1H Residual dipolar coupling analysis of native and alkaline-K79A Saccharomyces cerevisiae cytochrome c. Biophysical journal 2003, 84:3917-3923.
• [23]Tian F, Valafar H, Prestegard JH: A dipolar coupling based strategy for simultaneous resonance assignment and structure determination of protein backbones. J Am Chem Soc 2001, 123:11791-11796.
• [24]Chen K, Tjandra N: The use of residual dipolar coupling in studying proteins by NMR. Top curr chem 2012, 326:47-67.
• [25]Kummerlöwe G, Luy B: Residual dipolar couplings as a tool in determining the structure of organic molecules. TrAC Trends Anal Chem 2009, 28:483-493.
• [26]Thiele CM: Residual dipolar couplings (RDCs) in organic structure determination. Eur J Org Chem 2008, 2008:5673-5685.
• [27]Prestegard JH, Mayer KL, Valafar H, Benison GC: Determination of protein backbone structures from residual dipolar couplings. Meth Enzymol 2005, 394:175-209.
• [28]Bryson M, Tian F, Prestegard JH, Valafar H: REDCRAFT: a tool for simultaneous characterization of protein backbone structure and motion from RDC data. J Magn Reson (San Diego, Calif.: 1997) 2008, 191:322-334.
• [29]Wang X, Tash B, Flanagan JM, Tian F: RDC derived protein backbone resonance assignment using fragment assembly. J Biomol NMR 2011, 49:85-98.
• [30]Shealy P, Liu Y, Simin M, Valafar H: Backbone resonance assignment and order tensor estimation using residual dipolar couplings. J Biomol NMR 2011, 50:357-369.
• [31]Bailor MH, Musselman C, Hansen AL, Gulati K, Patel DJ, Al-Hashimi HM: Characterizing the relative orientation and dynamics of RNA A-form helices using NMR residual dipolar couplings. Nat Protoc 2007, 2:1536-1546.
• [32]Stelzer AC, Frank AT, Bailor MH, Andricioaei I, Al-Hashimi HM: Constructing atomic-resolution RNA structural ensembles using MD and motionally decoupled NMR RDCs. Methods (San Diego, Calif.) 2009, 49:167-173.
• [33]Shealy P, Simin M, Park SH, Opella SJ, Valafar H: Simultaneous structure and dynamics of a membrane protein using REDCRAFT: membrane-bound form of Pf1 coat protein. J Magn Reson (San Diego, Calif.: 1997) 2010, 207:8-16.
• [34]Liu Y, Kahn RA, Prestegard JH: Dynamic structure of membrane-anchored Arf*GTP. Nat Struct Mol Biol 2010, 17:876-881.
• [35]Prestegard JH, Al-Hashimi HM, Tolman JR: NMR structures of biomolecules using field oriented media and residual dipolar couplings. Q Rev Biophys 2000, 33:371-424.
• [36]Wang J, Walsh JD, Kuszewski J, Wang Y-X: Periodicity, planarity, and pixel (3P): a program using the intrinsic residual dipolar coupling periodicity-to-peptide plane correlation and phi/psi angles to derive protein backbone structures. J Magn Res (San Diego, Calif.: 1997) 2007, 189:90-103.
• [37]Prestegard JH, Kishore AI: Partial alignment of biomolecules: an aid to NMR characterization. Curr Opin Chem Biol 2001, 5:584-590.
• [38]Prestegard JH, Bougault CM, Kishore AI: Residual dipolar couplings in structure determination of biomolecules. Chem Rev 2004, 104:3519-3540.
• [39]Liu Y, Prestegard JH: A device for the measurement of residual chemical shift anisotropy and residual dipolar coupling in soluble and membrane-associated proteins. J Biomol NMR 2010, 47:249-258.
• [40]Kovacs H, Moskau D, Spraul M: Cryogenically cooled probes—a leap in NMR technology. Prog Nucl Magn Reson Spectrosc 2005, 46:131-155.
• [41]Schwieters CD, Kuszewski JJ, Tjandra N, Clore GM: The Xplor-NIH NMR molecular structure determination package. J Magn Reson 2003, 160:65-73.
• [42]Brunger AT, Adams PD, Clore GM, DeLano WL, Gros P, Grosse-Kunstleve RW, Jiang JS, Kuszewski J, Nilges M, Pannu NS, Read RJ, Rice LM, Simonson T, Warren GL, Brünger AT: Crystallography & NMR system: a new software suite for macromolecular structure determination. Acta crystallographica. Section D, Biological crystallography 1998, 54:905-921.
• [43]Güntert P: Automated NMR structure calculation with CYANA. Methods Mol Biol 2004, 278:353-378.
• [44]Güntert P, Mumenthaler C, Wüthrich K: Torsion angle dynamics for NMR structure calculation with the new program DYANA. J Mol Biol 1997, 273:283-298.
• [45]Navarro-Vázquez A: MSpin-RDC. A program for the use of residual dipolar couplings for structure elucidation of small molecules. Magnetic resonance in chemistry: MRC 2012, 50(Suppl 1):S73-S79.
• [46]Salomon-Ferrer R, Case DA, Walker RC: An overview of the Amber biomolecular simulation package. Wiley Interdisciplinary Reviews: Computational Molecular Science 2013, 3:198-210.
• [47]Hess B, Kutzner C, van der Spoel D, Lindahl E: GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 2008, 4:435-447.
• [48]Valafar H, Prestegard JH: REDCAT: a residual dipolar coupling analysis tool. J Magn Reson (San Diego, Calif.: 1997) 2004, 167:228-241.
• [49]Zweckstetter M: NMR: prediction of molecular alignment from structure using the PALES software. Nat Protoc 2008, 3:679-690.
• [50]Warren JJ, Moore PB: A maximum likelihood method for determining D(a)(PQ) and R for sets of dipolar coupling data. J Magn Reson (San Diego, Calif.: 1997) 2001, 149:271-275.
• [51]Losonczi JA, Andrec M, Fischer MW, Prestegard JH: Order matrix analysis of residual dipolar couplings using singular value decomposition. J Magn Reson (San Diego, Calif.: 1997) 1999, 138:334-342.
• [52]Mukhopadhyay R, Miao X, Shealy P, Valafar H: Efficient and accurate estimation of relative order tensors from lambda-maps. J Magn Reson (San Diego, Calif.: 1997) 2009, 198:236-247.
• [53]Miao X, Mukhopadhyay R, Valafar H: MR&VH MX: estimation of relative order tensors, and reconstruction of vectors in space using unassigned RDC data and its application. J Magn Reson (San Diego, Calif.: 1997) 2008, 194:202-211.
• [54]Valafar H, Prestegard JH: Rapid classification of a protein fold family using a statistical analysis of dipolar couplings. Bioinformatics (Oxford, England) 2003, 19:1549-1555.
• [55]Koradi R, Billeter M, Wuthrich K: MOLMOL: A program for display and analysis of macromolecular structures. J Mol Graphics 1996, 14:51-55.
• [56]DeLano WL: Use of PYMOL as a communications tool for molecular science. Abstracts Of Papers Of The American Chemical Society 2004, 228:U313-U314.
• [57]Humphrey W, Dalke A, Schulten K: VMD: visual molecular dynamics. J Mol Graph 1996, 14:27-28. 33–38
• [58]Bax A, Kontaxis G, Tjandra N: Dipolar couplings in macromolecular structure determination. Methods in enzymology 2001, 339:127-174.
• [59]Saupe A, Englert G: High-resolution nuclear magnetic resonance spectra of orientated molecules. Phys Rev Lett 1963, 11:462-464.
• [60]Greshenfeld NA: The Nature of Mathematical Modeling. Cambridge, UK: Cambridge University Press; 1998.
• [61]Press WH, Teukolsky SA, Vettering WT, Flannery BP: Numerical Recipes in C++: The Art of Scientific Computing (2nd edn) 1 Numerical Recipes Example Book (C++) (2nd edn) 2 Numerical Recipes Multi-Language Code CD ROM with LINUX or UNIX Single-Screen License Revised Version 3. Eur J Phys 2003, 24:329-330.
• [62]Wang J, Valafar H, Prestegard JH: Assessment of protein alignment using 1H-1H residual dipolar coupling measurements. J Magn Reson 2005, 172:85-90.
• [63]Sánchez-Pedregal VM, Santamaría-Fernández R, Navarro-Vázquez A: Residual dipolar couplings of freely rotating groups in small molecules. Stereochemical assignment and side-chain conformation of 8-phenylmenthol. Organic letters 2009, 11:1471-1474.
• [64]Racine J: gnuplot 4.0: a portable interactive plotting utility. J Appl Econ 2006, 21:133-141.
• [65]Delaglio F, Kontaxis G, Bax A: Protein structure determination using molecular fragment replacement and NMR dipolar couplings. J Am Chem Soc 2000, 122:2142-2143.
• [66]Al-Hashimi HM, Valafar H, Terrell M, Zartler ER, Eidsness MK, Prestegard JH: Variation of molecular alignment as a means of resolving orientational ambiguities in protein structures from dipolar couplings. J Magn Reson (San Diego, Calif.: 1997) 2000, 143:402-406.
• [67]Tolman JR, Al-Hashimi HM, Kay LE, Prestegard JH: Structural and dynamic analysis of residual dipolar coupling data for proteins. J Am Chem Soc 2001, 123:1416-1424.
• [68]Phillips JC, Braun R, Wang W, Gumbart J, Tajkhorshid E, Villa E, Chipot C, Skeel RD, Kale L, Schulten K: Scalable molecular dynamics with NAMD. J Comput Chem 2005, 26:1781-1802.
• [69]Schwieters CD, Kuszewski JJ, Clore GM: Using Xplor-NIH for NMR molecular structure determination. Progress in Nuclear Magnetic Resonance Spectroscopy 2006, 48:47-62.
• [70]XPLOR Interface Manual. http://nmr.cit.nih.gov/xplor-nih/ webcite
• [71]Schwieters CD, Clore GM: The VMD-XPLOR visualization package for NMR structure refinement. J Magn Reson 2001, 149:239-244.
• [72]Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The protein data bank. Nucleic Acids Res 2000, 28:235-242.
• [73]Ulrich EL, Akutsu H, Doreleijers JF, Harano Y, Ioannidis YE, Lin J, Livny M, Mading S, Maziuk D, Miller Z, Nakatani E, Schulte CF, Tolmie DE, Kent Wenger R, Yao H, Markley JL: BioMagResBank. Nucleic acids research 2008, 36:D402-D408.
• [74]Doreleijers JF, Mading S, Maziuk D, Sojourner K, Yin L, Zhu J, Markley JL, Ulrich EL: BioMagResBank database with sets of experimental NMR constraints corresponding to the structures of over 1400 biomolecules deposited in the Protein Data Bank. J Biomol NMR 2003, 26:139-146.
• [75]Eberstadt M, Huang B, Chen Z, Meadows RP, Ng SC, Zheng L, Lenardo MJ, Fesik SW: NMR structure and mutagenesis of the FADD (Mort1) death-effector domain. Nature 1998, 392:941-945.
• [76]Ulmer TS, Ramirez BE, Delaglio F, Bax A: Evaluation of backbone proton positions and dynamics in a small protein by liquid crystal NMR spectroscopy. J Am Chem Soc 2003, 125:9179-9191.
• [77]Carreras CW, Santi DV: The catalytic mechanism and structure of thymidylate synthase. Annu Rev of Bioch 1995, 64:721-762.
• [78]Harrison PT, Scott JE, Hutchinson MJ, Thompson R: Site-directed mutagenesis of varicella-zoster virus thymidylate synthase. Analysis of two highly conserved regions of the enzyme. Eur J Biochem / FEBS 1995, 230:511-516.
• [79]Phan J, Steadman DJ, Koli S, Ding WC, Minor W, Dunlap RB, Berger SH, Lebioda L: Structure of human thymidylate synthase suggests advantages of chemotherapy with noncompetitive inhibitors. J Biol Chem 2001, 276:14170-14177.
• [80]Schiffer CA, Clifton IJ, Davisson VJ, Santi DV, Stroud RM: Crystal structure of human thymidylate synthase: a structural mechanism for guiding substrates into the active site. Biochemistry 1995, 34:16279-16287.
• [81]Phan J, Koli S, Minor W, Dunlap RB, Berger SH, Lebioda L: Human thymidylate synthase is in the closed conformation when complexed with dUMP and raltitrexed, an antifolate drug. Biochemistry 2001, 40:1897-1902.
• [82]Berger SH, Berger FG, Lebioda L: Effects of ligand binding and conformational switching on intracellular stability of human thymidylate synthase. Biochimica et biophysica acta 2004, 1696:15-22.
• [83]Valafar H, Simin M, Irausquin S: A review of REDCRAFT: simultaneous investigation of structure and dynamics of proteins from RDC restraints. Annual Reports on NMR Spectroscopy 2012, 76:23-66.