Paul K. Weiner

A distance geometry study of ring systems : Application to cyclooctane, 18-crown-6, cyclododecane and androstanedione

Abstract We present the application of distance geometry methods to the generation of structures of a sampling of organic molecules: cyclooctane, cyclododecane, 18-crown-6, and androstane-3,17-dione. The method provides a simple, convenient method to generate either a random sample of molecular conformations, or to generate specified conformations. Using this approach, we found a new, relatively low-energy conformation of 18-crown-6. We also demonstrated that the lowest energy structure of cyclododecane was not exactly of D 4 symmetry, which had been previously assumed in molecular mechanics optimization.

Reduced variable molecular dynamics

This article describes an extension to previously developed constraint techniques. These enhanced constraint methods will enable the study of large computational chemistry problems that cannot be easily handled with current constrained molecular dynamics (MD) methods. These methods are based on an O(N) solution to the constrained equations of motion. The benefits of this approach are that (1) the system constraints are solved exactly at each time step, (2) the solution algorithm is noniterative, (3) the algorithm is recursive and scales as O(N), (4) the algorithm is numerically stable, (5) the algorithm is highly amenable to parallel processing, and (6) potentially greater integration step sizes are possible. It is anticipated that application of this methodology will provide a 10‐ to 100‐improvement in the speed of a large molecular trajectory as compared with the time required to run a conventional atomistic unconstrained simulation. It is, therefore, anticipated that this methodology will provide an enabling capacity for pursuing the drug discovery process for large molecular systems.

A conformational analysis of daunomycin considering D-ring repucker.

We present a complete molecule mechanics optimization of daunomycin. Two different D-ring puckers are found to be of comparable energy, consistent with NMR data, although only one of these low-energy structures has been observed by X-ray crystallography. Our results are more consistent with the previous conformational analysis of daunomycin by Neidle and Taylor (Neidle, S. and Taylor, G.L. (1979) FEBS Lett. 107, 348-354) than that of Nakata and Hopfinger (Nakata, Y. and Hopfinger, A.J. (1980) FEBS Lett. 117, 259-264).