Biomedical Engineering Reference
In-Depth Information
Protein Structure
Knowledge of protein structure is generally considered a prerequisite to understanding protein
function and, by extension, a cornerstone of proteomics research. Because months and sometimes
years are involved in verifying protein structure through experimental methods, computational
methods of modeling and predicting protein structure are currently viewed as the only viable means
of quickly determining the structure of a newly discovered protein. This section explores the role of
modeling and simulation methods in determining protein structure.
Proteins, like genes, don't exist as linear sequences of molecules, but assume complex, compact 3D
shapes. Protein shapes or configurations are characterized as secondary, tertiary, or quaternary. The
primary protein configuration—the simple linear sequence of covalently bound amino acids—is
functionally uninteresting. The secondary structure is the local geometry along the sequence,
typically in the form of sheets, coils, loops, and helices. Most proteins are composed of a combination
of secondary structures. A protein's tertiary structure describes how the molecule folds in 3D space.
Quaternary structure describes the complex configuration of a protein that is interacting with other
molecules in 3D space.
There are two main computational alternatives to experimental methods of determining or predicting
secondary and tertiary protein structures from sequence data. The first approach is based on ab initio
methods, which involve reasoning from first principles. The second approach, often termed heuristic
methods, is based on some form of pattern matching, using knowledge of existing protein structures.
Ab initio methods rely on molecular physics, and ignore any relationship of the molecule with other
proteins. Heuristic methods, in contrast, use information contained in known protein structures.
Figure 9-11
shows a flowchart of the methods available for determining or predicting protein
structure from protein sequence data.
Figure 9-11. Computational Methods of Protein Structure Prediction versus
Experimental Protein Structure Determination Methods. Ab initio and
heuristic methods promise to provide less accurate but more timely results,
compared to experimental methods that can require a year or more of
research per molecule.
