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Computes the change in deltaSconf_folding caused by formation of the disulfide bonds in a given topology. S_conf refers to the configurational entropy of the protein chain only.
deltaS_conf_folding = S_conf_folded - S_conf_unfolded
Disulfide formation restricts the conformational freedom of the denatured state, decreasing S_conf_unfolded, which increases deltaS_conf_folding.
deltaG_folding = deltaH_folding - T (deltaS_conf_folding + deltaS_other)
A more positive deltaS_conf_folding leads to greater stability of the folded state (a more negative deltaG_folding).
The change in deltaS_conf_folding caused by a particular disulfide configuration is computed based on modeling the denatured state of the protein using random flight configurational statistics according to a Gaussian approximation. For an overview and the equations themselves, see "Analysis and Classification of Disulphide Connectivity in Proteins: The Entropic effect of Cross-Linkage", PM Harrison & MJE Sternberg, J Mol Biol 1994 244, 448-463 .
Briefly,
deltaS_conf_folding = - ln (Pn) P_n = (deltaV (3/(2*pi*(b^2)))^(3/2))^n |A_n|^(3/2)
where:
Topologies will pass the filter if the change in deltaS_conf_folding caused by the disulfide configuration is higher (more positive) than a fixed threshold ( lower_bound
), and more positive than a chain length- and number of disulfide-dependent threshold. The chain length- and disulfide-dependent threshold was computed by surveying natural proteins with 3-5 disulfides and 60 or fewer residues, and is computed as:
threshold = (0.1604 * residues) + (1.7245 * disulfides) + 5.1477 + tightness
where tightness
is user specified. Larger values for tightness lead to a higher (and thus looser) threshold. With a tightness of zero, 61% of natural proteins pass the filter. With a tightness of 1, 82% of natural proteins pass the filter, and with a tightness of -1, only 19% of natural proteins pass the filter.
<DisulfideEntropy name="&string" tightness="(0 &Real)" lower_bound="(0 &Real)"/>