Abstract
BackgroundThe number of available structures of large multi-protein assemblies is quite small. Such structures provide phenomenal insights on the organization, mechanism of formation and functional properties of the assembly. Hence detailed analysis of such structures is highly rewarding. However, the common problem in such analyses is the low resolution of these structures. In the recent times a number of attempts that combine low resolution cryo-EM data with higher resolution structures determined using X-ray analysis or NMR or generated using comparative modeling have been reported. Even in such attempts the best result one arrives at is the very course idea about the assembly structure in terms of trace of the Cα atoms which are modeled with modest accuracy.Methodology/Principal FindingsIn this paper first we present an objective approach to identify potentially solvent exposed and buried residues solely from the position of Cα atoms and amino acid sequence using residue type-dependent thresholds for accessible surface areas of Cα. We extend the method further to recognize potential protein-protein interface residues.Conclusion/ SignificanceOur approach to identify buried and exposed residues solely from the positions of Cα atoms resulted in an accuracy of 84%, sensitivity of 83–89% and specificity of 67–94% while recognition of interfacial residues corresponded to an accuracy of 94%, sensitivity of 70–96% and specificity of 58–94%. Interestingly, detailed analysis of cases of mismatch between recognition of interface residues from Cα positions and all-atom models suggested that, recognition of interfacial residues using Cα atoms only correspond better with intuitive notion of what is an interfacial residue. Our method should be useful in the objective analysis of structures of protein assemblies when positions of only Cα positions are available as, for example, in the cases of integration of cryo-EM data and high resolution structures of the components of the assembly.
Highlights
Chemical nature and structural context of residues in a protein generate diversity in the contribution of residues towards stability and function of the protein [1]
A structure in which the atomic level models are embedded in the low resolution maps obtained from cryoelectron microscopy studies is reliable typically only upto the level of Ca trace
Classification of residues as surface exposed and buried using solely the positions of Ca atoms is highly obscure as the solvent accessibility-based [12] recognition of exposed and buried residues in proteins [2,13,14,15,16,17,18,19,20] rely on the availability of side chain positions
Summary
Chemical nature and structural context of residues in a protein generate diversity in the contribution of residues towards stability and function of the protein [1]. Uncertainty in the positions of main chain atoms and the sidechains is high Often in such modeling studies, the structures of proteins are made available only up to the Ca level. In the recent times a number of attempts that combine low resolution cryo-EM data with higher resolution structures determined using X-ray analysis or NMR or generated using comparative modeling have been reported. Even in such attempts the best result one arrives at is the very course idea about the assembly structure in terms of trace of the Ca atoms which are modeled with modest accuracy
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