Conserved water mediated H-bonding dynamics of Ser117 and Thr119 residues in human transthyretin-thyroxin complexation: inhibitor modeling study through docking and molecular dynamics simulation.

Transthyretin (TTR) is a protein whose aggregation and deposition causes amyloid diseases in human beings. Amyloid fibril formation is prevented by binding of thyroxin (T4) or its analogs to TTR. The MD simulation study of several solvated X-ray structures of apo and holo TTR has indicated the role of a conserved water molecule and its interaction with T4 binding residues Ser117 and Thr119.

Conserved water-mediated H-bonding dynamics of catalytic His159 and Asp158: insight into a possible acid-base coupled mechanism in plant thiol protease.

Cysteine protease is ubiquitous in nature. Excess activity of this enzyme causes intercellular proteolysis, muscle tissue degradation, etc. The role of water-mediated interactions in the stabilization of catalytically significant Asp158 and His159 was investigated by performing molecular dynamics simulation studies of 16 three-dimensional structures of plant thiol proteases.

Structural insight to mutated Y116S transthyretin by molecular dynamics simulation.

Familial amyloidotic polyneuropathy (FAP) is strictly associated with point mutations of transthyretin (TTR) protein. The Tyr116-->Ser (Y116S) mutant TTR is an important amyloidogenic variant responsible for FAP. Structural dynamics of monomeric TR and its mutant (Y116S) may give some clue relating to amyloid formation.

Conserved water-mediated H-bonding dynamics of catalytic Asn 175 in plant thiol protease.

The role of invariant water molecules in the activity of plant cysteine protease is ubiquitous in nature. On analysing the 11 different Protein DataBank (PDB) structures of plant thiol proteases, the two invariant water molecules W1 and W2 (W220 and W222 in the template 1PPN structure) were observed to form H-bonds with the O b atom of Asn 175. Extensive energy minimization and molecular dynamics simulation studies up to 2 ns on all the PDB and solvated structures clearly revealed the involvement of the H-bonding association of the two water molecules in fixing the orientation of the asparagine residue of the catalytic triad.