Structural bases of lectin-carbohydrate affinities: Comparison with protein-folding energetics

We have made a comparative structure based analysis of the thermodynamics o f lectin-carbohydrate (L-C) binding and protein folding. Examination of the total change in accessible surface area in those processes revealed a much larger decrease in free energy per unit of area buried in the case of L-C associations. According to our analysis, this larger stabilization of L-C i nteractions arises from a more favorable enthalpy of burying a unit of pola r surface area, and from higher proportions of polar areas. Hydrogen bonds present at 14 L-C interfaces were identified, and their overall characteris tics were compared to those reported before for hydrogen bonds in protein s tructures. Three major factors might explain why polar-polar interactions a re stronger in L-C binding than in protein folding: (1) higher surface dens ity of hydrogen bonds; (2) better hydrogen-bonding geometry; (3) larger pro portion of hydrogen bonds involving charged groups. Theoretically, the bind ing entropy can be partitioned into three main contributions: entropy chang es due to surface desolvation, entropy losses arising from freezing rotatab le bonds, and entropic effects that result from restricting translation and overall rotation motions. These contributions were estimated from structur al information and added up to give calculated binding entropies. Good corr elation between experimental and calculated values was observed when solvat ion effects were treated according to a parametrization developed by other authors from protein folding studies. Finally, our structural parametrizati on gave calculated free energies that deviate from experimental values by 1 .1 kcal/mol on the average; this amounts to an uncertainty of one order of magnitude in the binding constant.