Insights into the structure and energetics of proteins and nucleic acids from molecular dynamics simulations

Nan-jie Deng, Ph.D.
Senior scientist
Accelrys Inc., San Diego, CA

北京大学新生物楼610
2006年3月31日(星期五)上午10:00

Abstract

Molecular dynamics simulations and related computational techniques are increasingly being used in structural biology and biochemistry, and are frequently able to obtain information at atomistic details which are difficult to access by experimental methods. Here we present results from two recent molecular dynamics studies on proteins and nucleic acids. In the first case study, the molecular mechanism for the Cu2+ binding induced destabilization of β2-microglobulin is investigated. The destabilization of the protein is linked to the fibril formation in dialysis-related amyloidosis (DRA), a serious medical condition. Computer simulations show a correlation between the contents of bound Cu2+ ions and protein flexibility, and provide insights into the molecular driving forces for the destabilization. The second part of the talk is concerned with the structure and energetics of a RNA hairpin sequence which exhibits interesting conformational transitions in solution. Computer simulations in explicit and continuum solvents were performed to study the energetics of various forms of the RNA. The results from free energy calculations using the MM-PBSA method demonstrated a shift in the conformational equilibria from the duplex to the hairpin form, when the temperature is increased from 276 K to 300 K, in good agreement with experiment. The single stranded RNA has more favorable vibrational entropy than the other two forms, but is less stable than the hairpin by about 20 kcal/mol. The results are discussed in relation to recent NMR and thermodynamics studies.