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. 2015 Feb 10;11(2):609-22.
doi: 10.1021/ct500864r.

Combined covalent-electrostatic model of hydrogen bonding improves structure prediction with Rosetta

Matthew J O'Meara  1 , Andrew Leaver-Fay, Michael D Tyka, Amelie Stein, Kevin Houlihan, Frank DiMaio, Philip Bradley, Tanja Kortemme, David Baker, Jack Snoeyink, Brian Kuhlman
Affiliations

Combined covalent-electrostatic model of hydrogen bonding improves structure prediction with Rosetta

Matthew J O'Meara et al. J Chem Theory Comput. .

Abstract

Interactions between polar atoms are challenging to model because at very short ranges they form hydrogen bonds (H-bonds) that are partially covalent in character and exhibit strong orientation preferences; at longer ranges the orientation preferences are lost, but significant electrostatic interactions between charged and partially charged atoms remain VSports手机版. To simultaneously model these two types of behavior, we refined an orientation dependent model of hydrogen bonds [Kortemme et al. J. Mol. Biol. 2003, 326, 1239] used by the molecular modeling program Rosetta and then combined it with a distance-dependent Coulomb model of electrostatics. The functional form of the H-bond potential is physically motivated and parameters are fit so that H-bond geometries that Rosetta generates closely resemble H-bond geometries in high-resolution crystal structures. The combined potentials improve performance in a variety of scientific benchmarks including decoy discrimination, side chain prediction, and native sequence recovery in protein design simulations and establishes a new standard energy function for Rosetta. .

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Figure 1
Figure 1
H-bond degrees of freedom in HBv2 are defined on the Acceptor BBase, Base, and Acceptor atoms and the Donor Hydrogen and Donor atoms, depending on the chemical types (S.4.1).
Figure 2
Figure 2
The hBAH,BAχ2 functional form for sp2 acceptors avoids a numeric instability in BAχ at BAH angle 180°, by smoothly interpolating between in-plane (A) and out-of-plane (B) BAH potentials as a function of BAχ (C): hBAH,BAχ2. The Lambert-azimuthal projection of hBAH1 (from HBv1) (D), hBAH,BAχ2 (from HBv2) (E) and 3d rendering of EHBv2 (F) with a linear AHD and contoured at [−1.2,−1.0, and − .78] shows that HBv2 describes two symmetric lobes corresponding to the ideal sp2 orbitals, while HBv1 does not.
Figure 3
Figure 3
H-bond geometries for Asp and Glu acceptors paired with charged donors from native protein structures and models created with different energy functions: Elec, HBv1, HBv2 and ElecHBv2. For each cell, the Lambert-azimuthal projection of the conditional (BAH, BAχ) feature density is estimated and scaled to the range [0,1].
Figure 4
Figure 4
Geometries of backbone-backbone H-bonds. Lambert azimuthal projection of BAH, BAχ feature density for α-helices, residue pairs with sequence separation greater than 5 (LongRange), anti-parallel and parallel β-sheets by sample source (columns). The Native-LongRange interactions show a distinctive “beetle” shape that we sought to recapitulate with HBv2.
Figure 5
Figure 5
Serine hydrogen bonds. (A) Schematic of a serine hydroxyl group accepting an H-bond. Choices of the Base atom define the BAH angle; HBv2 uses Cβ (1), HBv1 uses H (2), and the visualization use V (3). (B) Lambert azimuthal projection of (BAH, BAχ) feature density for H-bonds with serine Acceptors, with SeqSep > 5.
Figure 6
Figure 6
H-bond distances (sequence separation greater than 5) as a function of donor type from native protein structures and models created with different energy functions.
Figure 7
Figure 7
AHdis vs AHD scatter plot for Native hydroxyl-donor to backbone-acceptor polar contacts. The thin blue lines contour a kernel density estimation (KDE) of the points to show density otherwise obscured by overplotting. Note, due to boundary effects, the KDE underestimates the density at − cos(AHD) = 1.0. The dimensions are scaled so randomly placed contacts will have a uniform distribution.
Figure 8
Figure 8
Scientific benchmarks as a function of H-bond weight. Lower values indicate improved performance for the decoy discrimination test, while higher values indicate improved performance for the sequence recovery and rotamer recovery tests. Grey regions indicate 90% confidence interval for locally-weighted, degree-2 polynomial regression (loess). Based on these results ElecHBv2 with a weight of 0.8 was chosen as the preferred energy function.
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References

    1. Baker EN, Hubbard RE. Prog. Biophys. molec. Biol. 1984;44:97. - PubMed
    1. Fersht AR, Shi JP, Knill-Jones J, Lowe DM, Wilkinson AJ, Blow DM, Brick P, Carter P, Waye MMY, Winter G. Nature. 1985;314:235. - PubMed
    1. Müller-Dethlefs K, Hobza P. Chem. Rev. 2000;100:143. - PubMed
    1. Morozov AV, Kortemme T. Adv. Protein Chem. 2005;72:1. - PubMed
    1. Forrest R, Honig B. Proteins. 2005;61:296. - "VSports最新版本" PubMed