Molecular simulation of the folding patterns of the omega-loop (Tyr181 to Tyr188) of HIV-1 reverse transcriptase.

Abstract

A large, highly hydrophilic and constrained omega-loop was dissected from the allosteric area of HIV-1 reverse transcriptase (segment Tyr181 to Tyr188). The loop contains two amino acids (Asp185, Asp186) of the catalytic aspartyl triad (Asp110, Asp185, Asp186) and two amino acids (Tyr181, Tyr188) of the nonnucleoside RT inhibitor (NNRTI) binding sites. Hydrogen-bonding forces between the two folded peptide chains play the greatest role in holding the two chains together and in specifying the folding patterns. The treatment of solvents as dielectric continuums surrounding the AMBER force field model has shown changes in conformation but these changes were not dramatically because the omega-loop shape was completely maintained.