1. Identification of Helix-Turn-Helix (HTH) DNA-Binding Motifs
Changhui Yan
Department of Computer Science
Utah State University

2. HTH Motifs
Protein sequences sharing low similarities can fold into a similar HTH structure.
Identifying HTH motifs from sequence is extremely challenging
7 families containing HTH motifs from the Pfam database. Positive data set: 2,198 proteins.
Negative data set: 1,518 proteins.

3. Combination of Amino Acid Sequence and Predicted Secondary Structure
LQQITHIANQL-GLE----KDVVRVWF
LQQITHIANQL-GLE----KDVVRVWF
HHHEEHEEEHMHE----HHEEMMEH
HMM_AA
HMM_AA_SS

4. Reduced Alphabets
Schemes for reducing amino acid alphabet based on the BLOSUM50 matrix by Henikoff and Henikoff (1992) derived by grouping and averaging the similarity matrix elements as described in the text. (Murphy et al. 2000)

5. Results Table 1. Cross-Families Evaluations True Positive 1
False Positive 2
HMM_AA 3
HMM_AA_SS
(20 letters) 3
227
(Murphy_15) 3
474
(Murphy_10) 3
470
(Murphy_8) 3
431 5
True positive: HTH motifs that are correctly identified as such.
False positive: Non-HTH motifs that are identified as HTH motifs.
The alphabet used to encode amino acid sequences.

6. Results
Table 2. Comparisons with a method based on profile-profile comparisons
Total HTH motifs
FFAS03 and HMM_AA_SS
FFAS03 only
HMM_AA_SS only
563
135 24 71
Table 3. Putative HTH motifs in Ureaplasma parvum
Protein
Location
Annotation from Uniprot
sp|Q9PQE5|SCPB_UREPA
Participates to chromosomal partition during cell division
sp|Q9PQV6|RPOB_UREPA
DNA-directed RNA polymerase
sp|Q9PR27|SYY_UREPA
Tyrosyl-tRNA synthetase
sp|Q9PQC2|SYA_UREPA
Alanyl-tRNA synthetase
sp|Q9PQ74|DPO3A_UREPA
DNA polymerase III subunit alpha
sp|Q9PQX7|Y166_UREPA
Hypothetical protein