ROSETTA search al algorithm Monte Carlo/ simulated Annealing Structures are assembled from fragments by Begin with a fully extended chain Randomly replace the conformation of one 9 residue segment with the conformation of one of its neighbors in the library Evaluate the move: Accept or reject based on an energy function Make another random move After a prescribed number of cycles switch to 3- residue fragment moves
ROSETTA search algorithm Monte Carlo/Simulated Annealing • Structures are assembled from fragments by: – Begin with a fully extended chain – Randomly replace the conformation of one 9 residue segment with the conformation of one of its neighbors in the library – Evaluate the move: Accept or reject based on an energy function – Make another random move… – After a prescribed number of cycles, switch to 3- residue fragment moves
ROSETTA scoring function p(sequence structure p(structure sequence)=p(structure)x (sequence) sequence is constant need to estimate for decoys built from fragments Main contributions to P(structure) secondary structure packing (e.g. ensureβ- strands formβ- sheets Vdw packing Simons et al. PROTEINs(1999)34, 82-95
ROSETTA scoring function P (structure | sequence) = P (structure) × P ( sequence | structure ) P( sequence) sequence is constant need to estimate for decoys built from fragments Main contributions to P(structure) - secondary structure packing (e.g. ensure β-strands form β-sheets) - VdW packing Simons et al. PROTEINS (1999) 34, 82-95
Native-like structures have characteristic secondary structure packing Example: b-strand dipeptide vector Simons, KT, I Ruczinski, C Kooperberg, BA Fox, C Bystroff, and D Baker. "Improved Recognition of Native-like Protein Structures using A Combination of Sequence-dependent and Sequence-independent Features of Proteins. "Proteins 34, no. 1(1 January 1999): 82-95
Native-like structures have characteristic secondary structure packing Example: b-strand dipeptide vector Simons, KT, I Ruczinski, C Kooperberg, BA Fox, C Bystroff, and D Baker. "Improved Recognition of Native-like Protein Structures using A Combination of Sequence-dependent and Sequence-independent Features of Proteins." Proteins 34, no. 1 (1 January 1999): 82-95
B-strand packing geometry can detect native-like structures Simons, KT, I Ruczinski, C Kooperberg, BA Fox, C Bystroff, and D Baker. "Improved Recognition of Native-like Protein Structures using A Combination of Sequence-dependent and Sequence- independent Features of Proteins. Proteins 34, no. 1(1 January 1999): 82-95
Simons, KT, I Ruczinski, C Kooperberg, BA Fox, C Bystroff, and D Baker. "Improved Recognition of Native-like Protein Structures using A Combination of Sequence-dependent and Sequence-independent Features of Proteins." Proteins 34, no. 1 (1 January 1999): 82-95. β-strand packing geometry can detect native-like structures
ROSETTA scoring function P(structure sequence)=P(structure)x p(sequence structure) sequence sequence is constant need to estimate for decoys built from fragments
ROSETTA scoring function P (structure | sequence) = P (structure) × P ( sequence | structure ) P( sequence) sequence is constant need to estimate for decoys built from fragments