Paper Citing NAMD - Abstract
Bairagya, Hridoy R.; Mukhopadhyay, Bishnu P.
An insight to the dynamics of conserved water-mediated salt bridge interaction and interdomain recognition in hIMPDH isoforms
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 31:788-808, JUL 1 2013
Inosine monophosphate dehydrogenase (IMPDH) is involved in de novo biosynthesis pathway of guanosine nucleotide. Type II isoform of this enzyme is selectively upregulated in lymphocytes and chronic myelogenous leukemia (CML) cells, and is an excellent target for antileukemic agent. The molecular dynamics simulation results (15ns) of three unliganded 1B3O, 1JCN, and 1JR1 structures have clearly revealed that I-N, I-C (N- and C-terminal of catalytic domains) and C-1, C-2 (cystathionine-beta-synthase-1 and 2) domains of IMPDH enzyme have been stabilized by six conserved water (center) mediated salt bridge interactions. These conserved water molecules could be involved in interdomain or intradomain recognition, intradomain coupling, and charge transfer processes. The binding propensity of cystathionine-beta-synthase domain to catalytic domain (through conserved water-mediated salt bridges) has provided a new insight to the biochemistry of IMPDH. Stereospecific interaction of I-N with C-2 domain through conserved water molecule (K109-W-II (1)-D215/D216) is observed to be unique in the simulated structure of hIMPDH-II. The geometrical/structural consequences and topological feature around the W-II (1) water center may be utilized for isoform specific inhibitor design for CML cancer. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at :JBSD:1
