Recent developments in structural proteomics for protein structure determination

Abstract

The major challenges in structural proteomics include identifying all the proteins on the genome-wide scale, determining their structure-function relationships, and outlining the precise three-dimensional structures of the proteins. Protein structures are typically determined by experimental approaches such as X-ray crystallography or nuclear magnetic resonance (NMR) spectroscopy. However, the knowledge of three-dimensional space by these techniques is still limited. Thus, computational methods such as comparative and de novo approaches and molecular dynamic simulations are intensively used as alternative tools to predict the three-dimensional structures and dynamic behavior of proteins. This review summarizes recent developments in structural proteomics for protein structure determination; including instrumental methods such as X-ray crystallography and NMR spectroscopy, and computational methods such as comparative and de novo structure prediction and molecular dynamics simulations.

Proteomics in human cancer research

“…Comparative methods are based on the observation that proteins with similar sequences almost always have similar structures. Comparative methods consist of four basic steps: (i) finding a template; (ii) sequence-template alignment; (iii) model building; and (iv) model assessment [82]. High-accuracy comparative models share more than 50% sequence identity to their templates.…”

Effect of pH, urea, peptide length, and neighboring amino acids on alanine α‐proton random coil chemical shifts

“…Most commonly protein structure information is determined through crystallography, 1,2 circular dichroism, 3 or nuclear magnetic resonance (NMR). 1,2,4,5 While each technique has its own unique advantages and disadvantages related to the nature of the protein, speed of data acquisition, and extent and type of information that can be obtained, NMR offers a distinctive advantage in that it is a technique that is frequently available to investigators at small institutions. Furthermore, partial structural information can be determined quickly by NMR using the Chemical Shift Index method (CSI).…”

Structure and Dynamics of Proteins from Nuclear Magnetic Resonance Spectroscopy

“…Crystallography begins with the expression and purification of the protein or proteins of interest. The subsequent step is to produce crystals of sufficient quality (at least 2.5Å), in order to obtain high-resolution data for structure determination (Liu & Hsu, 2005;Sali et al, 2003). Typical X-ray diffraction experiments require only a small single crystal sample (of a few micrometers) in order to physically interrupt the flow of X-rays from a source and cause them to scatter or diffract (Ooi, 2010).…”

“…This allows for the direct inference of the types and arrangements of atoms, molecules and/or ions, as well as bond lengths and angles within the crystal (Ooi, 2010). Crystallization is often regarded as a slow and resource-intensive method (Liu & Hsu, 2005). What's more, since crystallization conditions cannot be predetermined, it is often necessary to screen a wide range of conditions related to pH, salt, protein concentration, and cofactors (Liu & Hsu, 2005;Sali et al, 2003).…”

“…Crystallization is often regarded as a slow and resource-intensive method (Liu & Hsu, 2005). What's more, since crystallization conditions cannot be predetermined, it is often necessary to screen a wide range of conditions related to pH, salt, protein concentration, and cofactors (Liu & Hsu, 2005;Sali et al, 2003). Although recent technologies allowing for the use of smaller sample volumes has led to the automation of high-throughput crystallization, most structures will still require a great deal of time (sometimes as long as days or weeks) in order to produce a highresolution structure (Abola et al, 2000;Ooi, 2010;Sali et al, 2003).…”