期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：3
页码：1020-1025
DOI：10.1073/pnas.95.3.1020
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：By incorporating predicted secondary and tertiary restraints derived from multiple sequence alignments into ab initio folding simulations, it has been possible to assemble native-like tertiary structures for a test set of 19 nonhomologous proteins ranging from 29 to 100 residues in length and representing all secondary structural classes. Secondary structural restraints are provided by the PHD secondary structure prediction algorithm that incorporates multiple sequence information. Multiple sequence alignments also provide predicted tertiary restraints via a two-step process: First, seed side chain contacts are selected from a correlated mutation analysis, and then an inverse folding algorithm expands these seed contacts. The predicted secondary and tertiary restraints are incorporated into a lattice-based, reduced protein model for structure assembly and refinement. The resulting native-like topologies exhibit a coordinate root--mean-square deviation from native for the whole chain between 3.1 and 6.7 A, with values ranging from 2.6 to 4.1 A over {approx}80% of the structure. Overall, this study suggests that the use of restraints derived from multiple sequence alignments combined with a fold assembly algorithm is a promising approach to the prediction of the global topology of small proteins.
