|
Homology modeling is basically used for the prediction of protein structure and it
constructs an atomic resolution model of a protein from the amino acid residues of the query
sequence (Marti, 2000). Argininosuccinate lyase (ASAL) in Salmonella choleraesuis is responsible for the pathogenic activity in animals and humans. The cellular component of this
protein is the cytoplasm. It involves in the biological process of amino acid biosynthesis and
arginine biosysnthesis. The molecular function of this protein is arginino succinate lyase
activity. Salmonella is a genus of the family Enterobacteriaceae. The pathogen, Salmonella causes various diseases such as salmonellosis, gastroenteritis and food poisoning. Salmonellosis
is one of the most common and widely distributed food-borne diseases. It constitutes a
major public health burden and represents a significant cost in many countries. Millions of
human cases are reported worldwide every year and the disease results in thousands of
deaths. In the recent years, problems related to Salmonella have increased significantly both
in terms of incidence and severity of cases of human salmonellosis. Gastroenteritis
causes diarrhoea or vomiting with non-inflammatory infection of the upper small bowel
or inflammatory infection of the colon and in each part of the gastrointestinal tract.
Food poisoning is common, usually mild, but sometimes deadly illness. Typical symptoms
include nausea, vomiting, abdominal cramping, diarrhoea that come on sudden consumption of
a contaminated food or drink.
MODELLER implements comparative protein structure modeling by satisfaction
of spatial restraints that include (1) homology-derived restraints on the distances and
dihedral angles in the target sequence, extracted from its alignment with the template
structures; (2) stereochemical restraints such as bond length and bond angle preferences obtained
from the molecular mechanics force-field; (3) statistical preferences for dihedral angles and
non-bonded inter-atomic distances, obtained from a representative set of known
protein structures; and (4) optional manually curated restraints, such as those from
NMR spectroscopy, rules of secondary structure packing, etc. The spatial restraints, expressed
as probability density functions, are combined into an objective function that is optimized
by a combination of conjugate gradients and molecular dynamics with simulated
annealing. This model building procedure is similar to the structure determination by NMR spectroscopy. |
