Biomolecular Structure Determination

Morris, H. R. (1980). Biomolecular structure determination by mass spectrometry. Nature (London) 286, 447-452. 

Kolar M, Kubar T, Hobza P (2011) On the role of London dispersion forces in biomolecular structure determination. J Phys Chem B 115 8038-8046... 

The basic strategy for biomolecular structure determinations by NMR follows three stages ... 

Ordinarily, it is possible to distinguish between mm/rr and mr/rm triad stereosequences using standard NMR experiments, but distinction between the resonances of mm and rr triads can be made only if a spectrum from a stereoregular polymer of known relative configuration is available. Triple resonance 3D-NMR techniques combined with isotopic labelling have provided powerful tools for biomolecular structure determination which have tremendous potential applications in polymer chemistry [63-66]. 

Triple resonance 3D-NMR techniques combined with isotopic labelling have provided powerful tools for biomolecular structure determination [63-65] which have tremendous potential applications in polymer chemistry. 

AMU Bonvm, R Boelens, R Kaptem. Determination of biomolecular structures by NMR Use of relaxation matrix calculations. In WF van Gunsteren, PK Weiner, AI Wilkinson, eds. Computer Simulation of Biomolecular Systems Theoretical and Experimental Applications, Vol 2. Leiden ESCOM, 1993, pp 407-440. 

The introduction of instrumental methods of analysis and structure determination during the second half of the twentieth century transformed organic chemistry. [22] Freed from structural studies, some chemists concentrated on organic synthesis, others transferred their attention to biomolecular topics, and yet others switched to... 

R. Boelens, T. M. G. Koning, and R. Kaptein, J. Mol. Struct., 173, 299 (1988). Determination of Biomolecular Structures from Proton-Proton NOE s Using a Relaxation Matrix Approach. 

Application of NMR to three-dimensional structure determination is covered in several books, including NMR of Proteins and Nucleic Acids by Kurt Wiithrich,60 NMR of Proteins edited by G. M. Clore and A. M. Gronenborn,131 Biomolecular NMR Spectroscopy by Jeremy Evans,132 and Protein NMR Spectroscopy by John Cavanagh et al,120... 

Since conception over 100 years ago, MS has become an important analytical and research tool with diverse applications ranging from astronomical study of the solar system to materials analysis and process monitoring in chemical, oil and pharmaceutical industries. Use of MS has led to very many scientific breakthroughs including the discovery of isotopes, accurate determination of atomic mass, and the characterization of biomolecular structure. Indeed, MS is now a fundamental technique employed in pharmacology, toxicology and other biological, environmental and biomedical sciences. 

NMR is not a technique for everyday use in the biochemistry laboratory. The equipment needed for protein structure determination is expensive, and detailed expertise is needed to evaluate and interpret the results. For these reasons NMR as a tool in the study of biomolecular structure and function is confined to a limited number of specialist centres. 

Biomolecular NMR spectroscopy is applicable to both liquid-and solid-state samples. Liquid-state NMR spectroscopy, in which molecules are dissolved in a variety of different solvents and studied at ambient temperatures, is a powerful tool to derive information on the stmcture of proteins and nucleic acids, as well as their complexes with each other and small molecules, ions, and solvents. Liquid-state NMR can be applied not only to native folded states of proteins, but also to intrinsically unstmctured proteins as well as proteins in their unfolded state and under nonphysiological conditions (i.e., in organic solvents). Figure 1 provides an overview on the number of protein structures determined by liquid-state NMR spectroscopy. 

One important application of RDC measurements is the structural refinement of biomolecules that consist of several domains that are connected by more or less flexible linkers. Because of the flexibility of the linker and the distance between domains, J-couplings and NOE restraints will frequently not be sufficient for correct determination of the relative domain orientation. The addition of RDC restraints in structure calculation not only refines the biomolecular structure but also allows the relationship between structure and function to be studied. Interactions with other biomolecules and ligand binding may induce an intramolecular rearrangement of the relative orientation of domains that is detectable through RDC measurements (21, 22). 

Some Comments on Experimental Approaches to the Determination of Biomolecular Structure... 

Scattering methods for structure determination rely upon the availability of crystalline samples. On the other hand, NMR can make use of samples which have an isotropic orientation distribution and/or amorphous structures. This greater range of sample possibilities not only makes NMR applicable to studies of biomolecular structure with different macroscopic properties but also raises opportunities for different experimental procedures leading to increased amounts of structural information. However, attention must always be paid to the effect sample preparation may have on the conformation of the protein molecules relative to the naturally occurring strncmre. 

Although X-ray diffraction methods have proved to be extremely successful in the determination of a wide variety of biomolecular structures, including both globular and fibrous proteins and nucleic acids, polysaccharides and macromolecular assem-... 

This chapter introduces biomolecular structures from a hioinformatics perspective, with special emphasis on the sequences that are contained in three-dimensional structures. The major goal of this chapter is to inform the reader about the contents of structure database records and how they are treated, and sometimes mistreated, by popular software programs. This chapter does not cover the computational processes used by structural scientists to obtain three-dimensional structures, nor does it discuss the hner points of comparative protein architecture. Several excellent monographs regarding protein architecture and protein structure determination methods are already widely available and often found in campus bookstores (e.g., Branden and Tooze, 1999). 

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