Structural polymorphism of the HIV-1 leader region explored by computational methods.
Experimental studies revealed that the elements of the human immunodeficiency virus type 1 (HIV-1) 5'-untranslated leader region (5'-UTR) can fold in vitro into two alternative conformations, branched (BMH) and 'linearized' (LDI) and switch between them to achieve different functionality. In this study we computationally explored in detail, with our massively parallel genetic algorithm (MPGAfold), the propensity of 13 HIV-1 5'-UTRs to fold into the BMH and the LDI conformation types. Besides the BMH conformations these results predict the existence of two functionally equivalent types of LDI conformations. One is similar to what has been shown in vitro to exist in HIV-1 LAI, the other is a novel conformation exemplified by HIV-1 MAL long-distance interactions. These novel MPGAfold results are further corroborated by a consensus probability matrix algorithm applied to a set of 155 HIV-1 sequences. We also have determined in detail the impact of various strain mutations, domain sizes and folds of elongating sequences simulating folding during transcription on HIV-1 RNA secondary structure folding dynamics.
Kasprzak
Wojciech
W
Basic Research Program, SAIC Frederick, NCI-Frederick, Building 469, Room 150, Frederick, MD 21702, USA.
Bindewald
Eckart
E
Shapiro
Bruce A
BA
D020121:5' Untranslated Regions / Q000737:chemistry*; D000465:Algorithms; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods; D016384:Consensus Sequence; D015497:HIV-1 / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D012367:RNA, Viral / Q000737:chemistry*; D016415:Sequence Alignment; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic
D020121:5' Untranslated Regions; D012367:RNA, Viral