Fast accurate evaluation of protein solvent exposure.
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 A(2) to 3.70 A(2). This difference translates into a solvation energy difference of approximately 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.
Zhang
Naigong
N
Department of Physics, George Washington University, Washington, DC 20052, USA.
Zeng
Chen
C
Wingreen
Ned S
NS
D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D015195:Drug Design; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D012107:Research Design; D012680:Sensitivity and Specificity; D012997:Solvents / Q000737:chemistry / Q000378:metabolism*; D013499:Surface Properties; D013816:Thermodynamics; D013997:Time Factors
D011506:Proteins; D012997:Solvents