Paper Citing NAMD - Abstract
Wang, Zunliang; Han, Xiaofeng; He, Nongyue; Chen, Zhan; Brooks, Charles L., I.I.I.
Molecular Structures of C- and N-Terminus Cysteine Modified Cecropin P1 Chemically Immobilized onto Maleimide-Terminated Self-Assembled Mono layers Investigated by Molecular Dynamics Simulation
JOURNAL OF PHYSICAL CHEMISTRY B, 118:5670-5680, MAY 29 2014
Biosensors using peptides or proteins chemically immobilized on surfaces have many advantages such as better sensitivity, improved stability, and longer shelf life compared to those prepared using physically adsorbed biomolecules. Chemical immobilization can better control the interfacial conformation and orientation of peptides and proteins, leading to better activity of these biomolecules. In this research, molecular dynamics (MD) simulations were employed to systematically investigate the structure and dynamics of surface-tethered antimicrobial peptide cecropin P1 (CP1) modified with a cysteine residue at the C- (CP1c) or N-terminus (cCP1). Such CP1c and cCP1 molecules were chemically immobilized onto a silane-EG(4)-maleimide self-assembled monolayer (SAM) surface by forming a thio-ether bond between the cysteine group in CP1c or cCP1 and the surface maleimide group. The simulation results showed that the immobilized cCP1 (via the N-terminus) tends to bend and gradually lie down onto the SAM surface, due to the large structural fluctuation of the C-terminus induced by unfavorable interactions between the hydrophobic C-terminal residues and water. Differently, the tethered CP1c (via the C-terminus) more or less stands up on the surface, only tilting slightly even after 60 ns. The simulation results can be well correlated to the recent experimental results obtained from sum frequency generation (SFG) vibrational spectroscopic study. The current simulation data provide more atomic level details on how the hydrophobicity difference in the C-terminus and N-terminus of the amphiphilic peptide can lead to different structures of the same peptide tethered to the surface via different termini. This knowledge can be used to rationally design chemically immobilized peptides to achieve desired structure and functionality.
