Biology Reference
In-Depth Information
Chapter 17
PROMALS3D: Multiple Protein Sequence Alignment
Enhanced with Evolutionary and Three-Dimensional
Structural Information
Jimin Pei and Nick V. Grishin
Abstract
Multiple sequence alignment (MSA) is an essential tool with many applications in bioinformatics and
computational biology. Accurate MSA construction for divergent proteins remains a difficult computational
task. The constantly increasing protein sequences and structures in public databases could be used to
improve alignment quality. PROMALS3D is a tool for protein MSA construction enhanced with additional
evolutionary and structural information from database searches. PROMALS3D automatically identifies
homologs from sequence and structure databases for input proteins, derives structure-based constraints
from alignments of three-dimensional structures, and combines them with sequence-based constraints of
profile-profile alignments in a consistency-based framework to construct high-quality multiple sequence
alignments. PROMALS3D output is a consensus alignment enriched with sequence and structural infor-
mation about input proteins and their homologs. PROMALS3D Web server and package are available at
Key words
Multiple sequence alignment, Database searches, Three-dimensional structural alignment,
Consistency-based scoring, Probabilistic model of profile-profile alignment
1
Introduction
Multiple sequence alignment (MSA) is fundamentally important
for a variety of tasks in bioinformatics and computational biology,
including homology-based structure modeling, prediction of struc-
tural properties, sequence similarity searches, phylogenetic recon-
struction, and identification of functionally important sites. For a
set of protein sequences, MSA construction involves placement of
gap characters in sequences so that each position (column) contains
evolutionarily or structurally equivalent amino acid residues. Such a
biologically meaningful representation of multiple sequences not
only facilitates their visualization and inspection, but also helps
extraction of valuable information such as sequence conservation
and residue preferences on a positional basis.
