Optimal region of average side-chain entropy for fast protein folding

Search and study the general principles that govern kinetics and thermodyna mics of protein folding generates new insight into the factors that control this process. Here, we demonstrate based on the known experimental data an d using theoretical modeling of protein folding that side-chain entropy is one of the general determinants of protein folding. We show for proteins be longing to the same structural family that there exists an optimal relation ship between the average side-chain entropy and the average number of conta cts per residue for fast folding kinetics. Analysis of side-chain entropy f or proteins that fold without additional agents demonstrates that there exi sts an optimal region of average side-chain entropy for fast folding. Devia tion of the average side-chain entropy from the optimal region results in a n anomalous protein folding process (prions, a-lytic protease, subtilisin, some DNA-binding proteins). Proteins with high or low side-chain entropy wo uld have extended unfolded regions and would require some additional agents for complete folding. Such proteins are common in nature, and their struct ure properties have biological importance.