Structural polymorphism of the HIV-1 leader region explored by computational methods

作     者：Kasprzak, W Bindewald, E Shapiro, BA 

作者机构：NCI Frederick SAIC Frederick Basic Res Program Frederick MD 21702 USA NCI Frederick Natl Canc Inst Ctr Canc Res Nanbiol Program Frederick MD 21702 USA 

出 版 物：《NUCLEIC ACIDS RESEARCH》 (Nucleic Acids Res.)

年 卷 期：2005年第33卷第22期

页      面：7151-7163页

核心收录：

学科分类：0710[理学-生物学] 08[工学] 09[农学] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种] 

基　　金：Center for Cancer Research National Institutes of Health, NIH, (N01-C0-12400) National Institutes of Health, NIH National Cancer Institute, NCI 

主　　题：HUMAN-IMMUNODEFICIENCY-VIRUS PARALLEL GENETIC ALGORITHM RNA SECONDARY STRUCTURE PRIMER ACTIVATION SIGNAL DIMERIZATION INITIATION SITE IN-VITRO EVIDENCE REVERSE TRANSCRIPTION GENOMIC-RNA STRUCTURE PREDICTION PACKAGING SIGNAL Transcription Initiation Site computational methods LDI Reverse Transcription HIV-1 HIV 

摘      要：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.