Molecular dynamics simulation of the renin inhibitor H142 in water

✍ Scribed by Olle Teleman; Maria Lindberg; Sven Engström

• Book ID: 104631288
• Publisher: Springer Netherlands
• Year: 1991
• Tongue: English
• Weight: 962 KB
• Volume: 5
• Category: Article
• ISSN: 0920-654X
• DOI: 10.1007/bf00124338

✦ Synopsis

H 142 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 (H 142n) 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.