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PubMed · 11106167

Constraint-based assembly of tertiary protein structures from secondary structure elements.

K Yue·K A Dill
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Abstract

A challenge in computational protein folding is to assemble secondary structure elements-helices and strands-into well-packed tertiary structures. Particularly difficult is the formation of beta-sheets from strands, because they involve large conformational searches at the same time as precise packing and hydrogen bonding. Here we describe a method, called Geocore-2, that (1) grows chains one monomer or secondary structure at a time, then (2) disconnects the loops and performs a fast rigid-body docking step to achieve canonical packings, then (3) in the case of intrasheet strand packing, adjusts the side-chain rotamers; and finally (4) reattaches loops. Computational efficiency is enhanced by using a branch-and-bound search in which pruning rules aim to achieve a hydrophobic core and satisfactory hydrogen bonding patterns. We show that the pruning rules reduce computational time by 10(3)- to 10(5)-fold, and that this strategy is computationally practical at least for molecules up to about 100 amino acids long.

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AlgorithmsComputer GraphicsModels, MolecularModels, TheoreticalProtein ConformationProtein FoldingProtein Structure, SecondaryProtein Structure, TertiaryProteinsSoftwareJournal Article

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K Yue, K A Dill. 2000. Constraint-based assembly of tertiary protein structures from secondary structure elements.. https://pubmed.ncbi.nlm.nih.gov/11106167/

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