Taken together, our study showed that alanine substitutions at residue 271 or 274 of HIV-1 RT could cause conformational changes, rendering RT unstable and susceptible to viral protease. Thus, it is demonstrated that the ''turn'' (Gln 269 -Arg 277 ) between two helices may be important in maintaining protein stability and formation of bioactive dimer. Mutations in residues 271 and 274 of RT may inactivate the virus, which may enter cells but can not replicate. These findings may prove useful in anti-HIV drug design and vaccine development. Considering the emergence of resistance to the current RT inhibitors, this turn, especially amino acid residues 271 and 274, may be an ideal new target for antiviral drug design. The agents targeting this region may be able to affect the stability or dimerization of HIV-1 RT and subsequently inhibit viral replication. Moreover, the potential drug resistant mutations in this region, especially at residues 271 and 274, may probably inactivate the virus, which prevents the appearance of drugresistant virus. CVTree update: a newly designed phylogenetic study platform using composition vectors and whole genomes The CVTree web server (http://tlife.fudan.edu.cn/cvtree) presented here is a new implementation of the whole genome-based, alignment-free composition vector (CV) method for phylogenetic analysis. It is more efficient and user-friendly than the previously published version in the 2004 web server issue of Nucleic Acids Research. The development of whole genome-based alignment-free CV method has provided an independent verification to the traditional phylogenetic analysis based on a single gene or a few genes. This new implementation attempts to meet the challenge of ever increasing amount of genome data and includes in its database more than 850 prokaryotic genomes which will be updated monthly from NCBI, and more than 80 fungal genomes collected manually from several sequencing centers. This new CVTree web server provides a faster and stable research platform. Users can upload their own sequences to find their phylogenetic position among genomes selected from the server's; inbuilt database. All sequence data used in a session may be downloaded as a compressed file. In addition to standard phylogenetic trees, users can also choose to output trees whose monophyletic branches are collapsed to various taxonomic levels. This feature is particularly useful for comparing phylogeny with taxonomy when dealing with thousands of genomes. Traditional molecular phylogeny makes use of small subunit ribosomal RNA (SSU rRNA) sequences or a few orthologous proteins. Some more recent phylogenomic studies are based on concatenation of a larger number of proteins. The ever burgeoning genome sequencing projects worldwide have prompted several whole-genome phylogenetic approaches. However, most-if not all-rely on sequence alignment at some stage and therefore depend on many parameters, such as the use of scoring matrices. As modern prokaryotic and fungal taxonomy depends more and more on the traditional phylogeny, there is an urgent need to develop alternative approaches.