Search

The TT mismatch region in duplex d (CGCGATTCGCG) was studied using a 500-ps molecular dynamics (MD) simulation in water, and a series of 1-ps MD simulations and energy minimizations in vacuum. The DNA maintained its duplex structure, although the mismatch region showed significantly higher flexibility than the GC regions. The predominant conformation in the 500-ps MD simulation involved an average -42 degrees propeller twist between T6 and T'6, and a -22 degree buckle between A5 and T'7. One hydrogen bond was formed between T6 and T'6, and another between T6 and the O2 of T'7, with both Watson-Crick hydrogen bonds between A5 and T'7 remaining intact. The minimizations resulted in conformations with the equivalent hydrogen-bonding pattern, as well as ones with "wobble pair" hydrogen bonds between T6 and T'6. However, the wobble pair conformation was found to be unstable in the water simulation.

The rate constant for the transition between the equatorial and axial conformations of N-acetylalanyl-N'-methylamide has been determined from Langevin dynamics (LD) simulations with no explicit solvent. The isomerization rate is maximum at collision frequency gamma = 2 ps-1, shows diffusive character for gamma greater than or equal to 10 ps-1, but does not approach zero even at gamma = 0.01 ps-1. This behavior differs from that found for a one-dimensional bistable potential and indicates that both collisional energy transfer with solvent and vibrational energy transfer between internal modes are important in the dynamics of barrier crossing for this system. It is suggested that conformational searches of peptides be carried out using LD with a collision frequency that maximizes the isomerization rate (i.e., gamma approximately 2 ps-1). This method is expected to be more efficient than either molecular dynamics in vacuo (which corresponds to LD with gamma = 0) or molecular dynamics in solvent (where dynamics is largely diffusive).

Molecular dynamics using CHARMM and GEMM programs with the Star Technologies ST 100 array processor functioning at the speed of super computers was used as a searching algorithm for conformational exploration of the octapeptide Gly-Asn-Thr-Ile-Val-Ala-Glu. This poorly soluble octapeptide is the N-terminal epitope of an 11 KD glycoprotein antigen residing on human ductal carcinoma (breast) cells. Very long (nanoseconds) simulations were required. Both an alpha-helix and the N-acetyl-N1-methylamide derived minimized starting structures gave the same lowest potential energy conformation with simulations at 600 K. The same conformation was found only when using the latter starting conformation with simulations at 300 K. The lowest potential energy conformation was stabilized by 4 hydrophobic contacts and 13 H bonds completing one turn of a left-handed helix.