Abstract
This article focuses on the key step of obtaining the best possible sequence alignment of the Query (the protein you are interested in) to the Target (a protein of known three-dimensional structure) in order to build a molecular model for molecular replacement. Common sequence-alignment methods are discussed, starting from structural alignment and then moving to pairwise, multiple and profile-profile methods. The limitations of sequence-alignment methods and guidelines on how to judge the likely accuracy of alignment are considered. This is not a detailed tutorial on how to use specific programs; rather, the reader is directed to current tools and techniques that are likely to yield good results.
Highlights
A molecular-replacement search requires a model of the protein of interest
The first step in building the model is to identify one or more proteins of known threedimensional structure that are similar to the Query
A variation of up to 11.5% was observed for different Percentage identity’ (PID) calculations which increased to 22% when combined with different algorithms (Raghava & Barton, 2006)
Summary
A molecular-replacement search requires a model of the protein of interest (the Query). The first, and most important for molecular modelling, is to consider only the present-day sequences that are being aligned and the structural and functional importance of each amino acid in each protein. The second view of an alignment is based on the principle that present-day sequences have evolved from a common ancestor An alignment in this doi:10.1107/S0907444907046343 25 research papers context should reflect the process of mutation, insertion and deletion that has occurred over the course of evolution since the last common ancestor sequence. While this may produce a convincing alignment, it may not reproduce the best structural alignment as judged by present-day proteins. Before looking at this, we must first understand the challenges of protein structural alignment
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