Abstract
The segment Tyr181 to Tyr188 was dissected from the HIV-1 reverse transcriptase (RT). The segment contains two amino acids (Asp 185, Asp 186) of the catalytic aspartyl triad (Asp110, Asp185, Asp186) and two amino acids (Tyr181, Tyr188) of the nonnucleoside RT inhibitor (NNRTI) binding sites. In the quasicrystalline state, hydrogen-bonding forces between the folded peptide chain play the greatest role in holding two chains together and in specifying the folding pattern, an ω-loop. To surmount the energy-barrier height during the formation of an activated complex between certain amino acids of the ω-loop and ligands, the receptor must be in a fairly high-energy domain. This input of kinetic energy is simulated by molecular dynamics. Simulation of high and body temperatures “destroy” the hydrogen-bonding forces and therefore the ordered ω-loop conformation found by X-ray analysis (113 Kelvin temperature) and molecular modelling (near 0 Kelvin temperature). The conformational switching of Tyr181 is larger than that of Tyr188, allowing thus improved interactions with the aromatic residues of nonnucleoside inhibitors of the HIV-1 reverse transcriptase.