2.4 Methods and Algorithms
2.4.1 Sequence alignment and signal detection
A new method to detect remote relationships between protein sequences and known
three-dimensional structures based on direct energy calculations and without reliance on statistics has
been developed. The likelihood of a residue to occupy a given position on the structural template was
represented by an estimate of the stabilization free energy mad after explicit prediction of the
substituted side chain conformation. The profile matrix derive from these energy values and modified by
increasing the residue self-exchange values successfully predicted compatibility of heat-shock protein
and globin sequences with the three-dimensional structures of actin and phycocyanin, respectively,
from a full protein sequence databank search. The high sensitivity of the method makes it a unique tool
for predicting the three-dimensional fold for the rapidly growing number of protein sequences.
[Proteins - 1994]
