Comparative structural studies of T-20 analogues using molecular dynamics

The present study describes the results of two molecular dynamics simulations of 200 ns and 300 ns in implicit solvent of two anti-HIV peptide T-20 analogues of 42 (T-2042) and 36 residues (T-2036), respectively. Literature studies revealed an absence of NMR studies undertaken, due to poor solubility of the T-2036 peptide in water, in contrast to the T-2042 peptide where its NMR structure is well known. Accordingly this work was undertaken in two stages, the first involved a 200 ns MD study of a T-2042 peptide in accordance with the available experimental results, and the second stage involved an assessment of the conformational preferences of a T-2036 peptide from 300 ns MD trajectory. The solvent in both simulations was modeled using the Onufriev, Bashford and Case implementation of the Generalized Born procedure. Results obtained from both the trajectories revealed a remarkable difference in their secondary structural features. T-2042 exhibited well-defined α-helical region in the central part of peptide extending towards the C-terminal end, while the corresponding T-2036 peptide adopted turns and loops, in contrast to the reported NMR structure. The results obtained were further validated by two additional MD simulations starting from the helical structures of both the peptides.