This award will support collaborative research between Dr. Stephen Harvey, University of Alabama at Birmingham, and Dr. Richard Lavery, Institut de Biologie Physico-Chimique, Paris, France. The objective of the project is to study the nucleic acid double helix structure in terms of its primary base sequence. JUMNA (Junction Modeling of Nucleic Acids), a program developed by Dr. Lavery and his collaborators, is to be used to model various DNA structures. The program will also be modified to convert it from a structure optimization algorithm to a molecular dynamics algorithm. With regard to DNA structure, two classes of problems will be investigated. First, the relationship between DNA sequence and the variations in the local structure of the double helix will be examined, with the goal of understanding (1) the origins of DNA bending and (2) how proteins might recognize DNA sequences through subtle changes in structure. Second, models will be built for structures associated with polypurine-polypyrimidine sequences and with replication and transcription. Among the model structural elements will be stem-loop structures, single strands, helices containing two, three, and four strands, and the junctions between these various elements. These studies will be significant not only for the insights they provide into DNA structure, but because the methods developed will be useful for examining other modeling problems for both DNAs and RNAs. With the experience gained from these studies, the investigators will then turn to the problem of converting JUMNA into an algorithm for molecular dynamics simulations on nucleic acids. This latter project, if successful, would allow simulations to be performed on much larger systems and over much longer time scales than is possible with current molecular dynamics algorithms. The research groups headed by both Dr. Harvey and Dr. Lavery have made important contributions in the area of simulation of nucleic acids. Progress in simulation methods has been much slower for NAs than for proteins. The work done by these two groups is unique and an important contribution. The proposed collaboration is expected to accelerate progress in this field.

Project Start
Project End
Budget Start
1989-03-01
Budget End
1992-08-31
Support Year
Fiscal Year
1988
Total Cost
$10,648
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
DUNS #
City
Birmingham
State
AL
Country
United States
Zip Code
35294