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Structure and dynamics of α‐MSH using DRISM integral equation theory and stochastic dynamics
Author(s) -
Prabhu Ninad V.,
Perkyns John S.,
Pettitt B. Montgomery,
Hruby Victor J.
Publication year - 1999
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/(sici)1097-0282(199909)50:3<255::aid-bip3>3.0.co;2-v
Subject(s) - chemistry , molecular dynamics , side chain , salt bridge , langevin equation , integral equation , van der waals force , molecule , statistical physics , physics , computational chemistry , mathematical analysis , polymer , biochemistry , mathematics , organic chemistry , mutant , gene
The structural and dynamical features of the hormone α‐MSH in solution have been examined over a 100 ns time scale by using free energy molecular mechanics models at room temperature. The free energy surface has been modeled using methods from integral equation theory and the dynamics by the Langevin equation. A modification of the accessible surface area friction drag model was used to calculate the atomic friction coefficients. The molecule shows a stable β‐turn conformation in the message region and a close interaction between the side chains of His 6 , Phe 7 , and Trp 9 . A salt bridge between Glu 5 and Arg 8 was found not to be a preferred interaction, whereas a Glu 5 and Lys 11 salt bridge was not sampled, presumably due to relatively high free energy barriers. The message region was more conformationally rigid than the N‐terminal region. Several structural features observed here agree well with experimental results. The conformational features suggest a receptor–hormone interaction model where the hydrophobic side chains of Phe 7 and Trp 9 interact with the transmembrane portion of the MC1 receptor. Also, the positively charged side chain of Arg 8 and the imidazole side chain of His 6 may interact with the negatively charged portions of the receptor which may even be on the receptor's extracellular loops. © 1999 John Wiley & Sons, Inc. Biopoly 50: 255–272, 1999