Patent Document ID: 8374828
Application ID: 12344512
Patent Flag: 1

Claim One:
1. A computer-implemented method of ranking a generated ensemble of sequence to structure alignments by evaluating each for the presence of a targeted characteristic that affects the quantitative stability/flexibility relationships (QSFR) of the sequence to structure alignments, the method comprising using a computer to iteratively loop through the following steps: (i) selecting a target QSFR characteristic; (ii) selecting at least one set of target structures; (iii) generating a trial sequence to align to at least one of the target structures within the set of target structures; (iv) building model structures of the trial sequence for at least one subset of the set of target structures for use as templates; (v) running a distance constraint model against the model structures using probability distributions predicting the presence of at least one proximity state and at least one body bar network representing an ensemble of constraint topologies to obtain a QSFR characteristic for the templates; (vi) evaluating the output of the distance constraint model to determine the degree to which the model structures include the targeted QSFR characteristic; (vii) ranking the model structures against previously generated model structures, said ranking determined by the degree to which the respective model structures include the targeted QSFR characteristic; and (viii) repeating steps (i) to (vii) for a selected number of trial sequences; wherein the step of running a distance constraint model comprises: determining microscopic interaction types and proximity configurations of molecular constituents affecting thermodynamic properties of the model structure; calculating, for said at least one proximity state, a respective solvent entropy value, a respective solvent enthalpy value, and a respective conformational enthalpy value; calculating, for said at least one proximity state, a respective conformational entropy value, wherein calculating said respective conformational entropy value comprises the steps of (i) modeling constraints within the model structure using bars, wherein a probability that a bar is present (P) and a conditional probability for said bar to be an independent constraint (Q) are real numbers ranging from 0 to 1, and (ii) adding entropic contributions from bars representing independent constraints; selecting order parameters for constructing a free energy landscape, wherein groups of order parameters define nodes within the free energy landscape; determining, via a computer processor, a probability that a bar is present for said at least one proximity state; and calculating, via the computer processor, a minimum upper bound value for total free energy for a node in said proximity state, wherein said minimum upper bound value is based on P, Q, and the probability distribution for said proximity state, and wherein said minimum upper bound value for total free energy for said node is composed of a sum of said respective solvent entropy value, said respective solvent enthalpy value, said respective conformational enthalpy value, and said respective conformational entropy value.