Fast accurate evaluation of protein solvent exposure

Naigong Zhang, Chen Zeng, Ned S. Wingreen

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Protein solvation energies are often taken to be proportional to solvent-accessible surface areas. Computation of these areas is numerically demanding and may become a bottleneck for folding and design applications. Fast graph-based methods, such as dead-end elimination (DEE), become possible if all energies, including solvation energies, are expressed as single-residue and pair-residue terms. To this end, Street and Mayo originated a pair-residue approximation for solvent-accessible surface areas (Street AG, Mayo SL. Pairwise calculation of protein solvent accessible surface areas. Fold Des 1998;3:253-258). The dominant source of error in this method is the overlapping burial of side-chain surfaces in the protein core. Here we report a new pair-residue approximation, which greatly reduces this overlap error by the use of optimized generic side-chains. We have tested the generic-side-chain method for the ten proteins studied by Street and Mayo and for 377 single-domain proteins from the CATH database (Orengo CA, Michie AD, Jones S, Jones DT, Swindells MB, Thornton JM. CATH-A hierarchic classification of protein domain structures. Structure 1997;5:1093-1108). With little additional cost in computation, the new method consistently reduces error for total areas and residue-by-residue areas by more than a factor of two. For example, the residue-by-residue error (for buried area) is reduced from 7.42 Å2 to 3.70 Å2. This difference translates into a solvation energy difference of ∼0.2 kcal/mol per residue, amounting to a reduction in root-mean-square energy error of 2 kcal/mol for a 100 residue chain, a potentially critical difference for both protein folding and design applications.

Original languageEnglish (US)
Pages (from-to)565-576
Number of pages12
JournalProteins: Structure, Function and Genetics
Volume57
Issue number3
DOIs
StatePublished - Nov 15 2004

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Keywords

  • Dead-end elimination
  • Generic side-chains
  • Pair-wise surface area
  • Protein design
  • Solvent-accessible surface area

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