Protein aggregation prediction systems

A method of identifying one or more regions in the amino acid sequence of a protein which, in the folded protein, are predicted to promote aggregation, the method comprising:

• determining, for amino acid positions (i) along said sequence, a local propensity for aggregation (Ai) at a said amino acid position, said local propensity for aggregation being determined by a combination of a hydrophobicity value, an α-helix propensity value, a β-sheet propensity value, a charge value and a pattern value for said amino acid position;
• determining local structural stability values for said amino acid positions, a said local structural stability value comprising a measure of local structural stability at a said amino position;
• and
• combining said determined local propensities for aggregation at said amino acid positions and said local structural stability values at said amino acid positions to identify one or more regions in said amino acid sequence which, in said folded protein, are predicted to promote aggregation.

A carrier carrying computer program code for identifying one or more regions in the amino acid sequence of a protein which, in the folded protein, are predicted to promote aggregation, the code comprising code to:

• determine, for amino acid positions (i) along said sequence, a local propensity for aggregation (Ai) at a said amino acid position, said local propensity for aggregation being determined by a combination of a hydrophobicity value, an α-helix propensity value, a β-sheet propensity value, a charge value and a pattern value for said amino acid position;
• determine local structural stability values for said amino acid positions, a said local structural stability value comprising a measure of local structural stability at a said amino position;
• and
• combine said determined local propensities for aggregation at said amino acid positions and said local structural stability values at said amino acid positions to identify one or more regions in said amino acid sequence which, in said folded protein, are predicted to promote aggregation.

A method of identifying one or more regions in the amino acid sequence of a protein which, in the folded protein, are predicted to promote aggregation, the method comprising:

• determining, for a plurality of positions, i, along said sequence, a value of piagg, where piagg represents an intrinsic aggregation propensity of an amino acid at position i and comprises a function of ph, ps, phyd and pc and ph, ps, phyd and pc are, respectively, an α-helix propensity value, a β-sheet propensity value, a hydrophobicity value, and a charge value for an amino acid at a said position i along said sequence;
• determining, for a plurality of positions, i, along said sequence, a value of Aip, where Aip is determined from
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• denotes a first sum over amino acid positions in a first window to either side of position i, Iipat is a pattern value representing a pattern of one or both of hydrophilic and hydrophobic amino acids at position i, Iigk is a charge value representing a charge flanking or inside a said pattern, and wherein α1, αpat and αgk are scaling factors;
• and
• determining an aggregation propensity profile for said protein from values of Aip for said plurality of positions i along said sequence, said aggregation propensity profile comprising data identifying a variation of relative aggregation propensity with position along said sequence.

A method of determining the overall aggregation propensity of a folded protein, the method comprising:

• identifying one or more regions in the amino acid sequence of a protein which, in the folded protein, are predicted to promote aggregation taking into account one or both of a local hydrogen exchange and the suppression of an aggregation-inducing amino acid pattern by local charge;
• and then
• summing aggregation propensity data determined from values of a local propensity for aggregation (Ai) at a plurality of amino acid positions (i) along said sequence;
• wherein said summing comprises summing over substantially only said identified regions.