Molecular dynamics simulation of the renin inhibitor H142 in water.
H142 is a synthetic decapeptide designed to inhibit renin, an enzyme acting in the regulation of blood pressure. The inhibiting effect of H142 is caused by a reduction of a -Leu-Val-peptide bond (i. e. C(= O)-NH----CH2-NH). The conformational and dynamical properties of H142 and its unreduced counterpart (H142n) was modelled by means of molecular dynamics simulations. Water was either included explicitly in the simulations or as a dielectric continuum. When water molecules surround the peptides, they remain in a more or less extended conformation through the simulation. If water is replaced by a dielectric continuum, the peptides undergo a conformational change from an extended to a folded state. It is not clear whether this difference is a consequence of a too short simulation time for the water simulations, a force-field artifact promoting extended conformations, or if the extended conformation represents the true conformational state of the peptide. A number of dynamic properties were evaluated as well, such as overall rotation, translational diffusion, side-chain dynamics and hydrogen bonding.
Department of Physical Chemistry 2, Lund University, Sweden.
O
O
Teleman
M
M
Lindberg
S
S
Engström
D000595:Amino Acid Sequence; D000808:Angiotensinogen / Q000031:analogs & derivatives* / Q000737:chemistry; D003198:Computer Simulation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D000092502:Renin Inhibitors
D000808:Angiotensinogen; D000092502:Renin Inhibitors; C039583:H 142