Biology Reference
In-Depth Information
of known 3D structures by two orders of magnitude. Thus, no experi-
mental structure is available for the vast majority of protein sequences.
Therefore, the gap in structural knowledge must be bridged by compu-
tation. In this context, several computational methods for predicting the
3D structures of proteins have emerged and are the focus of many
research and service development efforts. In this chapter, we will describe
the approaches and services developed at the Swiss Institute of
Bioinformatics (SIB).
2. Protein Structure Prediction with
SWISS-MODEL — Methods and Tools
Prediction of the 3D structure of a protein from its amino acid sequence
remains a fundamental scientific problem, and it is considered as one of
the grand challenges in computational biology. Currently, comparative or
homology modeling, which uses experimentally elucidated structures of
related protein family members as templates to model the structure of the
protein of interest (the “target”), is the most accurate protein structure
modeling approach.
7,8
Template-based protein modeling techniques
exploit the evolutionary relationship between a target protein and tem-
plates with known experimental structures, based on the observation that
evolutionarily related sequences generally have similar 3D structures.
Most comparative modeling procedures consist of several consecutive
steps, which can be repeated iteratively until a satisfactory model is
obtained: (a) identification of suitable template structures related to the
target protein and the alignment of target and template(s) sequences;
(b) modeling of the structurally conserved regions and the prediction of
structurally variable regions; (c) refinement of the initial model; and
(d) evaluation of the resulting models. See Schwede
et al
.
9
and references
therein for details.
Protein modeling requires profound knowledge and understanding
of the rules underlying protein structure, suitable hardware and software,
as well as expert knowledge in their manipulation. As this combination is
not generally available in molecular biology laboratories, protein struc-
ture modeling is still not used to its full extent in biomedical research.
