The Impact of Interchain Hydrogen Bonding on b-Hairpin Stability is Readily Predicted by Molecular Dynamics Simulation

• Peptides are frequently used model systems for protein folding. They are also gaining increased importance as therapeutics. Here, the ability of molecular dynamics (MD) simulation for describing the structure and dynamics of β-hairpin peptides was investigated, with special attention given to the impact of a single interstrand sidechain to sidechain interaction. The MD trajectories were compared to structural information gained from solution NMR. By assigning frames from restraint-free MD simulations to an intuitive hydrogen bond on/off pattern, folding ratios and folding pathways were predicted. The computed molecular model successfully reproduces the folding ratios determined by NMR, indicating that MD simulation may be straightforwardly used as a screening tool in β-hairpin design.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Andra medicinska och farmaceutiska grundvetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Other Basic Medicine (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medicinal Chemistry (hsv//eng)

NATURVETENSKAP  -- Kemi -- Organisk kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Organic Chemistry (hsv//eng)

Nyckelord

peptid

hairpin

folding

molecular dynamics

hydrogen bond

conformation

beta-hairpin

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