Skip to main content

Interfacial Properties of Biomolecular Systems:Mechanism and Kinetics of Association and Melting


EMSL Project ID
34896

Abstract

The details of biomolecular recognition and interfacial interactions are integral components in association and dissociation and are fundamental to many aspects of biology and biotechnology. Missing are the molecular descriptions. For example, in the past, this laboratory has modeled DNA melting thermally, heating the systems to temperatures that would ensure duplex separation. But, in nature, the melting of DNA is not driven by heat; rather, enzymes and other proteins drive this process by shielding the molecule from the solvent and ions. In the case of the enzyme topoisomerase, the fundamental topological of the DNA is altered, the linking number Lk, i.e., the underwinding or overwinding of the DNA. The molecules find each other and function in complex and highly crowded environments. Recognition between the species occurs followed by binding, both specific and non-specific. In this project the focus will be on the kinetics and mechanism of the interfacial interactions of: i) the melting/dissociation of oligonucleotide systems, stress versus heat, ii) biomolecular association, the recognition and association of a protein/DNA system, and iii) atomic level description of RNA hairpin folding. All-atom molecular dynamics simulations will be used to study the melting of DNA. For the stress studies the calculations will be composed of a DNA duplex with at least three complete turns, in solution. Periodic boundary conditions will be used to connect the ends of the duplex at the edge of the simulation box and the linking number is altered by either adding base pairs to underwind the DNA or removing base pairs to overwind relative to the relaxed structure. The now familiar multiscale approach which uses data from calculations on a shorter length and time scale as input parameter for simulations at a longer time scale will be used to study the protein-DNA association. Brownian dynamics simulations coupled with all-atom molecular dynamics simulations will be used to understand the protein recognition and binding with DNA. Finally, the RNA hairpin folding studies will be performed with temperature-dependent replica exchange molecular dynamics simulations.

Project Details

Project type
Capability Research
Start Date
2009-10-01
End Date
2012-09-30
Status
Closed

Team

Principal Investigator

Bernard Pettitt
Institution
University of Texas Medical Branch

Team Members

Deepti Karandur
Institution
University of Texas Medical Branch

Christopher Myers
Institution
University of Texas Medical Branch

Joaquin Ambia Garrido
Institution
Baylor College of Medicine

E Zechiedrich
Institution
Baylor College of Medicine

Char Hu
Institution
University of Houston

Graham Randall
Institution
University of Houston

Bin Lin
Institution
University of Houston

Chuanying Chen
Institution
University of Texas Medical Branch

Kippi Dyer
Institution
University of Texas Medical Branch

Ka Yiu Wong
Institution
University of Texas Medical Branch

Gillian Lynch
Institution
University of Texas Medical Branch