Conformation Dependence of Backbone Geometry in Proteins

Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.
Structure (Impact Factor: 5.62). 10/2009; 17(10):1316-25. DOI: 10.1016/j.str.2009.08.012
Source: PubMed


Protein structure determination and predictive modeling have long been guided by the paradigm that the peptide backbone has a single, context-independent ideal geometry. Both quantum-mechanics calculations and empirical analyses have shown this is an incorrect simplification in that backbone covalent geometry actually varies systematically as a function of the phi and Psi backbone dihedral angles. Here, we use a nonredundant set of ultrahigh-resolution protein structures to define these conformation-dependent variations. The trends have a rational, structural basis that can be explained by avoidance of atomic clashes or optimization of favorable electrostatic interactions. To facilitate adoption of this paradigm, we have created a conformation-dependent library of covalent bond lengths and bond angles and shown that it has improved accuracy over existing methods without any additional variables to optimize. Protein structures derived from crystallographic refinement and predictive modeling both stand to benefit from incorporation of the paradigm.

Download full-text


Available from: Roland Dunbrack,

Click to see the full-text of:

Article: Conformation Dependence of Backbone Geometry in Proteins

2.68 MB

See full-text
  • Source
    • "Despite the impressive successes of protein crystallography, the methodological aspects related to the inclusion of these parameters in the refinement are still highly debated [51]–[53]. Our results support the idea that the context dependence of stereochemistry should be introduced in the refinement procedures of protein structures in order to enhance model accuracy [52], [54], [55]. In addition, the correlations here detected may be used as a validation tool for protein structures [26], [56]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: By combining quantum-mechanical analysis and statistical survey of peptide/protein structure databases we here report a thorough investigation of the conformational dependence of the geometry of peptide bond, the basic element of protein structures. Different peptide model systems have been studied by an integrated quantum mechanical approach, employing DFT, MP2 and CCSD(T) calculations, both in aqueous solution and in the gas phase. Also in absence of inter-residue interactions, small distortions from the planarity are more a rule than an exception, and they are mainly determined by the backbone ψ dihedral angle. These indications are fully corroborated by a statistical survey of accurate protein/peptide structures. Orbital analysis shows that orbital interactions between the σ system of C(α) substituents and the π system of the amide bond are crucial for the modulation of peptide bond distortions. Our study thus indicates that, although long-range inter-molecular interactions can obviously affect the peptide planarity, their influence is statistically averaged. Therefore, the variability of peptide bond geometry in proteins is remarkably reproduced by extremely simplified systems since local factors are the main driving force of these observed trends. The implications of the present findings for protein structure determination, validation and prediction are also discussed.
    PLoS ONE 09/2011; 6(9):e24533. DOI:10.1371/journal.pone.0024533 · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Persistent object stores have invoked much interest in recent years with the combination of the concepts of an object repository and the reuse of code and class definitions. One such store implemented at the University of Cape Town (UCT), exhibits the problems underlying most of these stores in that they require to have their own environment and open their own operating system, thus making them inaccessible to users on standard computer systems. Perhaps the most efficient methods of implementing such stores, in modern large address space computers uses memory mapping and distributed shared memory to provide access to the object store. Whereas if the use of memory mapping for objects is very efficient in a high speed local environment it presents problems when implemented over a wide area network. One alternative approach is the access of the object store by means of remote procedure calls to an object server. This paper describes work being undertaken to combine these two approaches by using the facilities provided by the OSF DCE to provide high reliability remote access, while using the distributed shared memory paradigm to provide high speed local access. The description of the object store and the access mechanisms using DCE are described
    Object Orientation in Operating Systems, 1993., Proceedings of the Third International Workshop on; 01/1994
  • [Show abstract] [Hide abstract]
    ABSTRACT: First wall protection against X-rays and debris coming from the pellet explosion is a critical design issue in inertial confinement fusion reactors. In the present communication, energy deposition of typical target X-ray in silicon-carbide and graphite is shown to occur over distances of the order of the first wall thickness for hard X-ray (γ-ray) target spectra, and the resulting maximum instantaneous temperature rise is negligible. It is also shown that, for photons with energies above 1 keV, large fraction of the target photon yield is deposited behind the first wall. Based on these results, it is concluded that target X-ray (γ-ray), which represent serious design constraint with metallic first walls, may be of less concern with first walls made of silicon-carbide or graphite. Consequently, the first wall protection scheme, based on silicon-carbide or graphite, needs to deal with potential first wall damage due to target debris only
    Fusion Engineering, 1995. SOFE '95. 'Seeking a New Energy Era'., 16th IEEE/NPSS Symposium; 01/1995
Show more