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Net Evolutionary Loss of Residue Polarity in Drosophilid Protein Cores Indicates Ongoing Optimization of Amino Acid Composition.

ABSTRACT: Amino acid frequencies in proteins may not be at equilibrium. We consider two possible explanations for the nonzero net residue fluxes in drosophilid proteins. First, protein interiors may have a suboptimal residue composition and be under a selective pressure favoring stability, that is, leading to the loss of polar (and the gain of large) amino acids. One would then expect stronger net fluxes on the protein interior than at the exposed sites. Alternatively, if most of the polarity loss occurs at the exposed sites and the selective constraint on amino acid composition at such sites decreases over time, net loss of polarity may be neutral and caused by disproportionally high occurrence of polar residues at exposed, least constrained sites. We estimated net evolutionary fluxes of residue polarity and volume at sites with different solvent accessibility in conserved protein families from 12 species of Drosophila. Net loss of polarity, miniscule in magnitude, but consistent across all lineages, occurred at all sites except the most exposed ones, where net flux of polarity was close to zero or, in membrane proteins, even positive. At the intermediate solvent accessibility the net fluxes of polarity and volume were similar to neutral predictions, whereas much of the polarity loss not attributable to neutral expectations occurred at the buried sites. These observations are consistent with the hypothesis that residue composition in many proteins is structurally suboptimal and continues to evolve toward lower polarity in the protein interior, in particular in proteins with intracellular localization. The magnitude of polarity and volume changes was independent from the protein's evolutionary age, indicating that the approach to equilibrium has been slow or that no such single equilibrium exists.

SUBMITTER: Yampolsky LY

PROVIDER: S-EPMC5737390 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Net Evolutionary Loss of Residue Polarity in Drosophilid Protein Cores Indicates Ongoing Optimization of Amino Acid Composition.

Yampolsky Lev Y LY Wolf Yuri I YI Bouzinier Michael A MA

Genome biology and evolution 20171001 10

Amino acid frequencies in proteins may not be at equilibrium. We consider two possible explanations for the nonzero net residue fluxes in drosophilid proteins. First, protein interiors may have a suboptimal residue composition and be under a selective pressure favoring stability, that is, leading to the loss of polar (and the gain of large) amino acids. One would then expect stronger net fluxes on the protein interior than at the exposed sites. Alternatively, if most of the polarity loss occurs ...[more]

PMID: 28985302

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Project description:Protein contact prediction helps reconstruct the tertiary structure that greatly determines a protein's function; therefore, contact prediction from the sequence is an important problem. Recently there has been exciting progress on this problem, but many of the existing methods are still low quality of prediction accuracy. In this paper, we present a new mixed integer linear programming (MILP)-based consensus method: a Consensus scheme based On a Mixed integer linear opTimization method for prOtein contact Prediction (COMTOP). The MILP-based consensus method combines the strengths of seven selected protein contact prediction methods, including CCMpred, EVfold, DeepCov, NNcon, PconsC4, plmDCA, and PSICOV, by optimizing the number of correctly predicted contacts and achieving a better prediction accuracy. The proposed hybrid protein residue-residue contact prediction scheme was tested in four independent test sets. For 239 highly non-redundant proteins, the method showed a prediction accuracy of 59.68%, 70.79%, 78.86%, 89.04%, 94.51%, and 97.35% for top-5L, top-3L, top-2L, top-L, top-L/2, and top-L/5 contacts, respectively. When tested on the CASP13 and CASP14 test sets, the proposed method obtained accuracies of 75.91% and 77.49% for top-L/5 predictions, respectively. COMTOP was further tested on 57 non-redundant ɑ-helical transmembrane proteins and achieved prediction accuracies of 64.34% and 73.91% for top-L/2 and top-L/5 predictions, respectively. For all test datasets, the improvement of COMTOP in accuracy over the seven individual methods increased with the increasing number of predicted contacts. For example, COMTOP performed much better for large number of contact predictions (such as top-5L and top-3L) than for small number of contact predictions such as top-L/2 and top-L/5. The results and analysis demonstrate that COMTOP can significantly improve the performance of the individual methods; therefore, COMTOP is more robust against different types of test sets. COMTOP also showed better/comparable predictions when compared with the state-of-the-art predictors.

Dataset Information

Net Evolutionary Loss of Residue Polarity in Drosophilid Protein Cores Indicates Ongoing Optimization of Amino Acid Composition.

Publications

Net Evolutionary Loss of Residue Polarity in Drosophilid Protein Cores Indicates Ongoing Optimization of Amino Acid Composition.

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