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Revised Backbone-Virtual-Bond-Angle Potentials to Treat the l- and d-Amino Acid Residues in the Coarse-Grained United Residue (UNRES) Force Field.

Sieradzan AK, Niadzvedtski A, Scheraga HA, Liwo A - J Chem Theory Comput (2014)

Bottom Line: Chem.The obtained results demonstrate that the UNRES force field with the new potentials reproduce the changes of free energies of helix formation upon d-substitution but overestimate the free energies of helix formation.UNRES was able to locate the native α-helical hairpin structure as the dominant structure even though no native sulfide-carbon bonds were present in the simulation.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Chemistry, University of Gdańsk , Wita Stwosza 63, 80-308 Gdańsk, Poland.

ABSTRACT
Continuing our effort to introduce d-amino-acid residues in the united residue (UNRES) force field developed in our laboratory, in this work the C(α) ··· C(α) ··· C(α) backbone-virtual-bond-valence-angle (θ) potentials for systems containing d-amino-acid residues have been developed. The potentials were determined by integrating the combined energy surfaces of all possible triplets of terminally blocked glycine, alanine, and proline obtained with ab initio molecular quantum mechanics at the MP2/6-31G(d,p) level to calculate the corresponding potentials of mean force (PMFs). Subsequently, analytical expressions were fitted to the PMFs to give the virtual-bond-valence potentials to be used in UNRES. Alanine represented all types of amino-acid residues except glycine and proline. The blocking groups were either the N-acetyl and N',N'-dimethyl or N-acetyl and pyrrolidyl group, depending on whether the residue next in sequence was an alanine-type or a proline residue. A total of 126 potentials (63 symmetry-unrelated potentials for each set of terminally blocking groups) were determined. Together with the torsional, double-torsional, and side-chain-rotamer potentials for polypeptide chains containing d-amino-acid residues determined in our earlier work (Sieradzan et al. J. Chem. Theory Comput., 2012, 8, 4746), the new virtual-bond-angle (θ) potentials now constitute the complete set of physics-based potentials with which to run coarse-grained simulations of systems containing d-amino-acid residues. The ability of the extended UNRES force field to reproduce thermodynamics of polypeptide systems with d-amino-acid residues was tested by comparing the experimentally measured and the calculated free energies of helix formation of model KLALKLALxxLKLALKLA peptides, where x denotes any d- or l- amino-acid residue. The obtained results demonstrate that the UNRES force field with the new potentials reproduce the changes of free energies of helix formation upon d-substitution but overestimate the free energies of helix formation. To test the ability of UNRES with the new potentials to reproduce the structures of polypeptides with d-amino-acid residues, an ab initio replica-exchange folding simulation of thurincin H from Bacillus thuringiensis, which has d-amino-acid residues in the sequence, was carried out. UNRES was able to locate the native α-helical hairpin structure as the dominant structure even though no native sulfide-carbon bonds were present in the simulation.

No MeSH data available.


Related in: MedlinePlus

Illustration of the modelterminally blocked tripeptides constructedto compute the integrals of eqs 3. Each X, Y,and Z denotes side-chains of l-Ala, d-Ala, Gly, l-Pro, or d-Pro.
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fig2: Illustration of the modelterminally blocked tripeptides constructedto compute the integrals of eqs 3. Each X, Y,and Z denotes side-chains of l-Ala, d-Ala, Gly, l-Pro, or d-Pro.

Mentions: The procedure developed in our earlierwork20 was used to determine new virtualCα ··· Cα ···Cα valence angle θ (Figure 2) bending potentials (Ub). In that procedure, therespective potentials of mean force (PMFs) were first calculated fromnonadiabatic energy maps of terminally blocked amino-acid residues,and then a three-dimensional Fourier series was fitted to them. Energymaps had been computed20 in the anglesof rotation λ(1) and λ(2) aboutthe virtual-bond Cα ··· Cα axes; these angles have been defined in ref (41) (Figure 3). Energy was minimized with respect to all degrees of freedomexcept for λ(1) and λ(2). Therefore,energy maps are minimized in the θ angle.


Revised Backbone-Virtual-Bond-Angle Potentials to Treat the l- and d-Amino Acid Residues in the Coarse-Grained United Residue (UNRES) Force Field.

Sieradzan AK, Niadzvedtski A, Scheraga HA, Liwo A - J Chem Theory Comput (2014)

Illustration of the modelterminally blocked tripeptides constructedto compute the integrals of eqs 3. Each X, Y,and Z denotes side-chains of l-Ala, d-Ala, Gly, l-Pro, or d-Pro.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4020588&req=5

fig2: Illustration of the modelterminally blocked tripeptides constructedto compute the integrals of eqs 3. Each X, Y,and Z denotes side-chains of l-Ala, d-Ala, Gly, l-Pro, or d-Pro.
Mentions: The procedure developed in our earlierwork20 was used to determine new virtualCα ··· Cα ···Cα valence angle θ (Figure 2) bending potentials (Ub). In that procedure, therespective potentials of mean force (PMFs) were first calculated fromnonadiabatic energy maps of terminally blocked amino-acid residues,and then a three-dimensional Fourier series was fitted to them. Energymaps had been computed20 in the anglesof rotation λ(1) and λ(2) aboutthe virtual-bond Cα ··· Cα axes; these angles have been defined in ref (41) (Figure 3). Energy was minimized with respect to all degrees of freedomexcept for λ(1) and λ(2). Therefore,energy maps are minimized in the θ angle.

Bottom Line: Chem.The obtained results demonstrate that the UNRES force field with the new potentials reproduce the changes of free energies of helix formation upon d-substitution but overestimate the free energies of helix formation.UNRES was able to locate the native α-helical hairpin structure as the dominant structure even though no native sulfide-carbon bonds were present in the simulation.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Chemistry, University of Gdańsk , Wita Stwosza 63, 80-308 Gdańsk, Poland.

ABSTRACT
Continuing our effort to introduce d-amino-acid residues in the united residue (UNRES) force field developed in our laboratory, in this work the C(α) ··· C(α) ··· C(α) backbone-virtual-bond-valence-angle (θ) potentials for systems containing d-amino-acid residues have been developed. The potentials were determined by integrating the combined energy surfaces of all possible triplets of terminally blocked glycine, alanine, and proline obtained with ab initio molecular quantum mechanics at the MP2/6-31G(d,p) level to calculate the corresponding potentials of mean force (PMFs). Subsequently, analytical expressions were fitted to the PMFs to give the virtual-bond-valence potentials to be used in UNRES. Alanine represented all types of amino-acid residues except glycine and proline. The blocking groups were either the N-acetyl and N',N'-dimethyl or N-acetyl and pyrrolidyl group, depending on whether the residue next in sequence was an alanine-type or a proline residue. A total of 126 potentials (63 symmetry-unrelated potentials for each set of terminally blocking groups) were determined. Together with the torsional, double-torsional, and side-chain-rotamer potentials for polypeptide chains containing d-amino-acid residues determined in our earlier work (Sieradzan et al. J. Chem. Theory Comput., 2012, 8, 4746), the new virtual-bond-angle (θ) potentials now constitute the complete set of physics-based potentials with which to run coarse-grained simulations of systems containing d-amino-acid residues. The ability of the extended UNRES force field to reproduce thermodynamics of polypeptide systems with d-amino-acid residues was tested by comparing the experimentally measured and the calculated free energies of helix formation of model KLALKLALxxLKLALKLA peptides, where x denotes any d- or l- amino-acid residue. The obtained results demonstrate that the UNRES force field with the new potentials reproduce the changes of free energies of helix formation upon d-substitution but overestimate the free energies of helix formation. To test the ability of UNRES with the new potentials to reproduce the structures of polypeptides with d-amino-acid residues, an ab initio replica-exchange folding simulation of thurincin H from Bacillus thuringiensis, which has d-amino-acid residues in the sequence, was carried out. UNRES was able to locate the native α-helical hairpin structure as the dominant structure even though no native sulfide-carbon bonds were present in the simulation.

No MeSH data available.


Related in: MedlinePlus