Journal
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
Volume 11, Issue 2, Pages 740-752Publisher
AMER CHEMICAL SOC
DOI: 10.1021/ct5008247
Keywords
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Funding
- North Carolina Biotechnology Center [2008MRG1102]
- National Science Foundation [CBET-0835794, MCB1101859, ACI-1053573]
- National Institutes of Health USA [EB006006, GM-23037]
- NSF's Research Triangle MRSEC [DMR-1121107]
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A search algorithm combining Monte Carlo, self-consistent mean field, and concerted rotation techniques was developed to discover peptide sequences that are reasonable HIV drug candidates due to their exceptional binding to human tRNA(UUU), the primer of HIV replication. The search algorithm allows for iteration between sequence mutations and conformation changes during sequence evolution. Searches conducted for different classes of peptides identified several potential peptide candidates. Analysis of the energy revealed that the asparagine and cysteine at residues 11 and 12 play important roles in recognizing tRNALys3 via van der Waals interactions, contributing to binding specificity. Arginines preferentially attract the phosphate linkage via chargecharge interaction, contributing to binding affinity. Evaluation of the RNA/peptide complexs structure revealed that adding conformation changes to the search algorithm yields peptides with better binding affinity and specificity to tRNALys3 than a previous mutation-only algorithm.
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