TY - JOUR
T1 - Prediction of polyelectrolyte polypeptide structures using Monte Carlo conformational search methods with implicit solvation modeling
AU - Evans, John Spencer
AU - Chan, Sunney I.
AU - Goddard, William A.
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1995/10
Y1 - 1995/10
N2 - Many interesting proteins possess defined sequence stretches containing negatively charged amino acids. At present, experimental methods (X‐ray crystallography, NMR) have failed to provide structural data for many of these sequence domains. We have applied the dihedral probability grid‐Monte Carlo (DPG‐MC) conformational search algorithm to a series of N‐ and C‐capped polyelectrolyte peptides, (Glu)20, (Asp)20. (PSer)20, and (PSer‐Asp)10, that represent polyanionic regions in a number of important proteins, such as parathymosin, calsequestrin, the sodium channel protein, and the acidic biomineralization proteins. The atomic charges were estimated from charge equilibration and the valence and van der Waals parameters are from DREIDING. Solvation of the carboxylate and phosphate groups was treated using sodium counterions for each charged side chain (one Na+ for COO−; two Na for CO(PO3)−2) plus a distance‐dependent (shielded) dielectric constant, ϵ = ϵ0R, to simulate solvent water. The structures of these polyelectrolyte polypeptides were obtained by the DPG‐MC conformational search with ϵ0 = 10, followed by calculation of solvation energies for the lowest energy conformers using the protein dipole‐Langevin dipole method of Warshel. These calculations predict a correlation between amino acid sequence and global folded conformational minima: Poly‐L‐Glu20, our structural benchmark, exhibited a preference for right‐handed α‐helix (47% helicity), which approximates experimental observations of 55–60% helicity in solution. For Asp‐ and PSer‐containing sequences, all conformers exhibited a low preference for right‐handed α‐helix formation (≤10%), but a significant percentage (?20% or greater) of β‐strand and β‐turn dihedrals were found in all three sequence cases: (1) Aspn forms supercoil conformers, with a 2:1:1 ratio of β‐turn:β‐strand:α‐helix dihedral angles; (2) PSer20 features a nearly 1:1 ratio of β‐turn:β‐sheet dihedral preferences, with very little preference for α‐helical structure, and possesses short regions of strand and turn combinations that give rise to a collapsed bend or hairpin structure; (3) (PSer‐Asp)10 features a 3:2:1 ratio of β‐sheet:β‐turn:α‐helix and gives rise to a superturn or C‐shaped structure.
AB - Many interesting proteins possess defined sequence stretches containing negatively charged amino acids. At present, experimental methods (X‐ray crystallography, NMR) have failed to provide structural data for many of these sequence domains. We have applied the dihedral probability grid‐Monte Carlo (DPG‐MC) conformational search algorithm to a series of N‐ and C‐capped polyelectrolyte peptides, (Glu)20, (Asp)20. (PSer)20, and (PSer‐Asp)10, that represent polyanionic regions in a number of important proteins, such as parathymosin, calsequestrin, the sodium channel protein, and the acidic biomineralization proteins. The atomic charges were estimated from charge equilibration and the valence and van der Waals parameters are from DREIDING. Solvation of the carboxylate and phosphate groups was treated using sodium counterions for each charged side chain (one Na+ for COO−; two Na for CO(PO3)−2) plus a distance‐dependent (shielded) dielectric constant, ϵ = ϵ0R, to simulate solvent water. The structures of these polyelectrolyte polypeptides were obtained by the DPG‐MC conformational search with ϵ0 = 10, followed by calculation of solvation energies for the lowest energy conformers using the protein dipole‐Langevin dipole method of Warshel. These calculations predict a correlation between amino acid sequence and global folded conformational minima: Poly‐L‐Glu20, our structural benchmark, exhibited a preference for right‐handed α‐helix (47% helicity), which approximates experimental observations of 55–60% helicity in solution. For Asp‐ and PSer‐containing sequences, all conformers exhibited a low preference for right‐handed α‐helix formation (≤10%), but a significant percentage (?20% or greater) of β‐strand and β‐turn dihedrals were found in all three sequence cases: (1) Aspn forms supercoil conformers, with a 2:1:1 ratio of β‐turn:β‐strand:α‐helix dihedral angles; (2) PSer20 features a nearly 1:1 ratio of β‐turn:β‐sheet dihedral preferences, with very little preference for α‐helical structure, and possesses short regions of strand and turn combinations that give rise to a collapsed bend or hairpin structure; (3) (PSer‐Asp)10 features a 3:2:1 ratio of β‐sheet:β‐turn:α‐helix and gives rise to a superturn or C‐shaped structure.
KW - Monte Carlo
KW - computational chemistry
KW - counterion condensation
KW - dihedral angles
KW - internal coordinate method
KW - peptide conformation
KW - polyanionic sequences
KW - protein conformation
KW - protein folding
UR - http://www.scopus.com/inward/record.url?scp=0028863591&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028863591&partnerID=8YFLogxK
U2 - 10.1002/pro.5560041007
DO - 10.1002/pro.5560041007
M3 - Article
C2 - 8535238
AN - SCOPUS:0028863591
VL - 4
SP - 2019
EP - 2031
JO - Protein Science
JF - Protein Science
SN - 0961-8368
IS - 10
ER -