The Use of Molecular Dynamics Simulations to Predict Thymine Dimer Formation in Histone Bound DNA
Date of Award
College of Arts & Sciences
Math & Science
Andrew T. Johnson
Thymine dimers are the major lesions in DNA that are caused by environmental conditions that can lead to apoptosis or can become carcinogenic (Schreier, et al., 2007). These dimers form when the pi electrons of one thymine in a neighboring thymine pair is excited by a photon from UV light, and occurs on the picosecond time scale (Schreier, et al., 2007). Due to the ultrafast nature of this reaction, the thymines must be in proper conformation prior to excitation in order for the reaction to take place. The proper conformation for the reaction has been found to occur when the C5-C5* and C6-C6* bond distances are below 3.5 Å (Johnson & Wiest, 2007) or below 4.2Å (Ramamurthy & Venkatesan, 1987) and the C5-C6-C5*-C6* dihedral bond angle is between 24 and 30 degrees (Johnson & Wiest, 2007). The objective of this study was to determine if the location of the neighboring thymines, as well as the presence of a dimer already within the system, plays a role in the formation of future dimers. In order to test this, molecular dynamics simulations were run on two systems, one without any dimers, one containing two dimers, both containing DNA wrapped around a protein histone octamer. Data on the distances, dihedral angles, and helicoidal parameters were all taken over the course of a 50ns simulation for both systems. The distances and dihedral angles were used to determine how often the neighboring thymines were in proper conformation in order for the reaction to occur. Our research indicates that the location of neighboring thymines around a protein histone octamer, as well as the presence of a dimer already within the system, affects the probability of future dimer formation.