Biomolecules encapsulated in carbon nanotubes (CNTs) have attracted much interest and facilitated exciting opportunities for biological and biomedical applications of CNTs. Understanding the fundamental interaction and change in biomolecules during encapsulation is indispensable but remains a challenge for both theoretical and experimental investigations. This paper focuses on the interaction between HIV replication inhibitor peptide (HRIP) and CNTs in a neutral solution with molecular dynamics simulation. We observed that HRIP spontaneously inserts into the CNTs and oscillates around the center of the tube, where the non-covalent interaction is minimum. The effects of the diameters of the CNTs on HRIP were investigated. The optimal diameter of the CNT that can provide the most effective encapsulation and causes minimum conformational change in HRIP was found. The present results provide valuable insights in the understanding of nanoscale drug delivery using CNT-based devices. (c) 2013 Elsevier B.V. All rights reserved.