Abstract
AMBER v. 4.1 force field in 1.5 ns NPT molecular dynamics simulations of murine epidermal growth factor (mEGF), human epidermal growth factor (hEGF), and human transforming growth factor-α (hTGF-α) structures with explicit TIP3P solvation were used to investigate differences in backbone stability, changes in secondary structure, interdomain flexibility, and weakly polar interactions. Backbone root mean square deviations of sections of each peptide show that the most stable regions in mEGF and hEGF are the A-, B-, and C-loops, whereas the most stable regions in hTGF-α are the A- and B- loops. The secondary structure in the B-loops of mEGF and hEGF differ significantly from the nuclear magnetic resonance (NMR) structures of mEGF and hEGF. The position and type of turns in the B-loop of mEGF and hEGF increase the interstrand distance of the antiparallel β-sheets thereby disrupting their structure. The interdomain flexibility of simulated hTGF-α structure is greater than in either mEGF or hEGF. The Φ, ψ dihedrals of hTGF-α occupy two distinct populations of phase space corresponding to either a C7/(eq) or an α-helical conformation. This change in dihedral angle is stabilized by Phe15 with Arg42 and Phe17 with Arg42 N-π weakly polar interactions that are present only in hTGF-α but not in mEGF or hEGF.
| Original language | English |
|---|---|
| Pages (from-to) | 396-407 |
| Number of pages | 12 |
| Journal | Proteins: Structure, Function and Genetics |
| Volume | 33 |
| Issue number | 3 |
| DOIs | |
| State | Published - Nov 15 1998 |
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All Science Journal Classification (ASJC) codes
- Genetics
- Structural Biology
- Biochemistry
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Molecular dynamics simulations of epidermal growth factor and transforming growth factor-α structures in water. / Watts, Charles R.; Lovas, Sándor; Murphy, Richard F.
In: Proteins: Structure, Function and Genetics, Vol. 33, No. 3, 15.11.1998, p. 396-407.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Molecular dynamics simulations of epidermal growth factor and transforming growth factor-α structures in water
AU - Watts, Charles R.
AU - Lovas, Sándor
AU - Murphy, Richard F.
PY - 1998/11/15
Y1 - 1998/11/15
N2 - AMBER v. 4.1 force field in 1.5 ns NPT molecular dynamics simulations of murine epidermal growth factor (mEGF), human epidermal growth factor (hEGF), and human transforming growth factor-α (hTGF-α) structures with explicit TIP3P solvation were used to investigate differences in backbone stability, changes in secondary structure, interdomain flexibility, and weakly polar interactions. Backbone root mean square deviations of sections of each peptide show that the most stable regions in mEGF and hEGF are the A-, B-, and C-loops, whereas the most stable regions in hTGF-α are the A- and B- loops. The secondary structure in the B-loops of mEGF and hEGF differ significantly from the nuclear magnetic resonance (NMR) structures of mEGF and hEGF. The position and type of turns in the B-loop of mEGF and hEGF increase the interstrand distance of the antiparallel β-sheets thereby disrupting their structure. The interdomain flexibility of simulated hTGF-α structure is greater than in either mEGF or hEGF. The Φ, ψ dihedrals of hTGF-α occupy two distinct populations of phase space corresponding to either a C7/(eq) or an α-helical conformation. This change in dihedral angle is stabilized by Phe15 with Arg42 and Phe17 with Arg42 N-π weakly polar interactions that are present only in hTGF-α but not in mEGF or hEGF.
AB - AMBER v. 4.1 force field in 1.5 ns NPT molecular dynamics simulations of murine epidermal growth factor (mEGF), human epidermal growth factor (hEGF), and human transforming growth factor-α (hTGF-α) structures with explicit TIP3P solvation were used to investigate differences in backbone stability, changes in secondary structure, interdomain flexibility, and weakly polar interactions. Backbone root mean square deviations of sections of each peptide show that the most stable regions in mEGF and hEGF are the A-, B-, and C-loops, whereas the most stable regions in hTGF-α are the A- and B- loops. The secondary structure in the B-loops of mEGF and hEGF differ significantly from the nuclear magnetic resonance (NMR) structures of mEGF and hEGF. The position and type of turns in the B-loop of mEGF and hEGF increase the interstrand distance of the antiparallel β-sheets thereby disrupting their structure. The interdomain flexibility of simulated hTGF-α structure is greater than in either mEGF or hEGF. The Φ, ψ dihedrals of hTGF-α occupy two distinct populations of phase space corresponding to either a C7/(eq) or an α-helical conformation. This change in dihedral angle is stabilized by Phe15 with Arg42 and Phe17 with Arg42 N-π weakly polar interactions that are present only in hTGF-α but not in mEGF or hEGF.
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U2 - 10.1002/(SICI)1097-0134(19981115)33:3<396::AID-PROT8>3.0.CO;2-I
DO - 10.1002/(SICI)1097-0134(19981115)33:3<396::AID-PROT8>3.0.CO;2-I
M3 - Article
C2 - 9829698
AN - SCOPUS:0032533398
VL - 33
SP - 396
EP - 407
JO - Proteins: Structure, Function and Genetics
JF - Proteins: Structure, Function and Genetics
SN - 0887-3585
IS - 3
ER -