Adding energy minimization strategy to peptide‐design algorithm enables better search for RNA‐binding peptides: Redesigned λ N peptide binds boxB RNA

• Published in: Journal of computational chemistry 2016-10, Vol.37 (27), p.2423-2435
• Main Authors: Xiao, Xingqing, Hung, Michelle E., Leonard, Joshua N., Hall, Carol K.
• Format: Article
• Language: English
• Subjects: Algorithms; energy minimization strategy; Molecular Dynamics Simulation; Peptide Library; Peptides - chemistry; peptide‐design algorithm; RNA tethering; RNA, Viral - chemistry; RNA-Binding Proteins - chemistry; RNA‐binding peptide; λ N peptide‐boxB RNA
• ISSN: 0192-8651; 1096-987X
• DOI: 10.1002/jcc.24466

Our previously developed peptide‐design algorithm was improved by adding an energy minimization strategy which allows the amino acid sidechains to move in a broad configuration space during sequence evolution. In this work, the new algorithm was used to generate a library of 21‐mer peptides which could substitute for λ N peptide in binding to boxB RNA. Six potential peptides were obtained from the algorithm, all of which exhibited good binding capability with boxB RNA. Atomistic molecular dynamics simulations were then conducted to examine the ability of the λ N peptide and three best evolved peptides, viz. Pept01, Pept26, and Pept28, to bind to boxB RNA. Simulation results demonstrated that our evolved peptides are better at binding to boxB RNA than the λ N peptide. Sequence searches using the old (without energy minimization strategy) and new (with energy minimization strategy) algorithms confirm that the new algorithm is more effective at finding good RNA‐binding peptides than the old algorithm. © 2016 Wiley Periodicals, Inc. A peptide‐design algorithm with a newly added energy minimization strategy was used to search for novel, high‐affinity peptides in substitution of the native λ N peptide to bind to boxB RNA. Atomistic molecular dynamics simulations were then employed to examine the binding ability of the native and the evolved peptides to the RNA target. Simulation results suggested that the improved algorithm enables better design of peptides to tether boxB RNA.