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Simulation study of the ability of a computationally‐designed peptide to recognize target tRNA Lys3 and other decoy tRNAs
Author(s) -
Xiao Xingqing,
Zhao Binwu,
Agris Paul F.,
Hall Carol K.
Publication year - 2016
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.3056
Subject(s) - transfer rna , decoy , van der waals force , molecular dynamics , chemistry , peptide , physics , crystallography , molecule , computational chemistry , quantum mechanics , rna , biochemistry , receptor , gene
In this paper, we investigate the ability of our computationally‐designed peptide, Pept10 (PNWNGNRWLNNCLRG), to recognize the anticodon stem and loop (ASL) domain of the hypermodified tRNA Lys3 (mcm 5 s 2 U 34 ,ms 2 t 6 A 37 ), a reverse transcription primer of HIV replication. Five other ASLs, the singly modified ASL Lys3 (ms 2 t 6 A 37 ), ASL Lys3 (s 2 U 34 ), ASL Lys3 (Ψ 39 ), ASL Lys1,2 (t 6 A 37 ), and ASL Glu (s 2 U 34 ), were used as decoys. Explicit‐solvent atomistic molecular dynamics simulations were performed to examine the process of binding of Pept10 with the target ASL Lys3 (mcm 5 s 2 U 34 ,ms 2 t 6 A 37 ) and the decoy ASLs. Simulation results demonstrated that Pept10 is capable of recognizing the target ASL Lys3 (mcm 5 s 2 U 34 ,ms 2 t 6 A 37 ) as well as one of the decoys, ASL Lys3 (Ψ 39 ), but screens out the other four decoy ASLs. The interchain van der Waals (VDW) and charge–charge (ELE + EGB) energies for the two best complexes were evaluated to shed light on the molecular recognition mechanism between Pept10 and ASLs. The results indicated that Pept10 recognizes and binds to the target ASL Lys3 (mcm 5 s 2 U 34 ,ms 2 t 6 A 37 ) through residues W 3 and R 7 which interact with the nucleotides mcm 5 s 2 U 34 , U 35 , and ms 2 t 6 A 37 via the interchain VDW energy. Pept10 also recognizes the decoy ASL Lys3 (Ψ 39 ) through residue R 14 which contacts the nucleotide U 36 via the interchain VDW energy. Regardless of the type of ASL, the positively charged arginines on Pept10 are attracted to the negatively charged phosphate linkages on the ASL via the interchain ELE + EGB energy, thereby enhancing the binding affinity.