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Polyproline II helix is the preferred conformation for unfolded polyalanine in water
Author(s) -
Mezei Mihaly,
Fleming Patrick J.,
Srinivasan Rajgopal,
Rose George D.
Publication year - 2004
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20050
Subject(s) - polyproline helix , solvation , conformational isomerism , solvation shell , chemistry , solvent models , peptide , water model , accessible surface area , aqueous solution , molecular dynamics , monte carlo method , solvent , solvophobic , crystallography , computational chemistry , solvent effects , helix (gastropod) , implicit solvation , free energy perturbation , molecule , organic chemistry , ecology , biochemistry , statistics , mathematics , snail , biology
Does aqueous solvent discriminate among peptide conformers? To address this question, we computed the solvation free energy of a blocked, 12‐residue polyalanyl‐peptide in explicit water and analyzed its solvent structure. The peptide was modeled in each of 4 conformers: α‐helix, antiparallel β‐strand, parallel β‐strand, and polyproline II helix (P II ). Monte Carlo simulations in the canonical ensemble were performed at 300 K using the CHARMM 22 forcefield with TIP3P water. The simulations indicate that the solvation free energy of P II is favored over that of other conformers for reasons that defy conventional explanation. Specifically, in these 4 conformers, an almost perfect correlation is found between a residue's solvent‐accessible surface area and the volume of its first solvent shell, but neither quantity is correlated with the observed differences in solvation free energy. Instead, solvation free energy tracks with the interaction energy between the peptide and its first‐shell water. An additional, previously unrecognized contribution involves the conformation‐dependent perturbation of first‐shell solvent organization. Unlike P II , β‐strands induce formation of entropically disfavored peptide:water bridges that order vicinal water in a manner reminiscent of the hydrophobic effect. The use of explicit water allows us to capture and characterize these dynamic water bridges that form and dissolve during our simulations. Proteins 2004. © 2004 Wiley‐Liss, Inc.