We present a protein fold recognition method that uses a comprehensive statistical interpretation of structural Hidden Markov Models (HMMs). The structure/fold recognition is done by summing the probabilities of all sequence-to-structure alignments Conventionally, Boltzmann statistics dictate that the optimal alignment can give an estimate of the lowest free energy of the sequence conformation imposed by the structural model. The alignment is optimized for a scoring function that is interpreted as a free energy of an amino acid in a structural environment. Near-optimal alignments are ignored, regardless of how likely they might be compared to the optimal alignment. Here we investigate an alternative view. A structure model can be seen as a statistical representation of an ensemble of similar structures. The optimal alignment is always the most probable, but sub-optimal alignments may have comparable probabilities. These sub-optimal alignments can be interpreted as optimal alignments to the “other” structures from the ensemble or optimal alignments under minor fluctuations in the scoring function. Summing probabilities for all alignments gives an estimate of sequence-model compatibility. We have built a set of structural HMMs for 188 protein structures, and have compared two methods for identifying the structure compatible with a sequence: by the optimal alignment probability and by the total probability. Fold recognition by total probability was 40% more accurate than fold recognition by the optimal alignment probability.

Article Free Access Share on A method for optimal design of a threading scoring function Authors: Jadwiga R. Bieńkowska BioMolecular Engineering Research Center, College of Engineering, Boston University, 36 Cummington Street, Boston, MA BioMolecular Engineering Research Center, College of Engineering, Boston University, 36 Cummington Street, Boston, MAView Profile , Robert G. Rogers BioMolecular Engineering Research Center, College of Engineering, Boston University, 36 Cummington Street, Boston, MA BioMolecular Engineering Research Center, College of Engineering, Boston University, 36 Cummington Street, Boston, MAView Profile , Temple F. Smith BioMolecular Engineering Research Center, College of Engineering, Boston University, 36 Cummington Street, Boston, MA BioMolecular Engineering Research Center, College of Engineering, Boston University, 36 Cummington Street, Boston, MAView Profile Authors Info & Claims RECOMB '99: Proceedings of the third annual international conference on Computational molecular biologyApril 1999 Pages 25–32https://doi.org/10.1145/299432.299446Published:01 April 1999Publication History 1citation7,945DownloadsMetricsTotal Citations1Total Downloads7,945Last 12 Months4Last 6 weeks2 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF

Article The threading approach to the inverse protein folding problem Share on Authors: Temple F. Smith BioMolecular Engineering Research Center, College of Engineering, Boston University, 36 Cummington Street, Boston, MA BioMolecular Engineering Research Center, College of Engineering, Boston University, 36 Cummington Street, Boston, MAView Profile , Loredana Lo Conte BioMolecular Engineering Research Center, College of Engineering, Boston University, 36 Cummington Street, Boston, MA and Department of Computer Science, College of Arts and Sciences, Boston University, Boston, MA BioMolecular Engineering Research Center, College of Engineering, Boston University, 36 Cummington Street, Boston, MA and Department of Computer Science, College of Arts and Sciences, Boston University, Boston, MAView Profile , Jadwiga Bienkowska BioMolecular Engineering Research Center, College of Engineering, Boston University, 36 Cummington Street, Boston, MA BioMolecular Engineering Research Center, College of Engineering, Boston University, 36 Cummington Street, Boston, MAView Profile , Bob Rogers BioMolecular Engineering Research Center, College of Engineering, Boston University, 36 Cummington Street, Boston, MA BioMolecular Engineering Research Center, College of Engineering, Boston University, 36 Cummington Street, Boston, MAView Profile , Chrysanthe Gaitatzes BioMolecular Engineering Research Center, College of Engineering, Boston University, 36 Cummington Street, Boston, MA BioMolecular Engineering Research Center, College of Engineering, Boston University, 36 Cummington Street, Boston, MAView Profile , Richard Lathrop Department of Infomation and Computer Science, University of California, Irvine, CA Department of Infomation and Computer Science, University of California, Irvine, CAView Profile Authors Info & Claims RECOMB '97: Proceedings of the first annual international conference on Computational molecular biologyJanuary 1997 Pages 287–292https://doi.org/10.1145/267521.267887Online:19 January 1997Publication History 3citation95DownloadsMetricsTotal Citations3Total Downloads95Last 12 Months3Last 6 weeks1 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access