Molecular dynamics simulations for the future : applications in nanotechnology and drug design

• Main Author: Elsheshiny, Asmaa Abdelghafar Ahmed
• Published: University of Leeds 2013
• Subjects: 539
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.659032

Molecular dynamics simulations can provide atomistic details of the dynamics of proteins over timescales in the range of pico to micro seconds, and is therefore complementary to experimental structural techniques such as X-ray crystallography, which only provides static information, and Nuclear Magnetic resonance (NMR), which does not provide fully atomistic detail. In this work atomistic molecular dynamics simulation has been used to investigate the electromechanical properties of three structurally distinct proteins, and has revealed that the conformational changes that occur are strongly dependent on the secondary structure of the protein. These calculations are of relevance to the many in vitro and in vivo situations where strong electric fields are experienced by proteins, such as during electroporation. We have also applied this technique to investigate the effect of electric fields on different polymorphs of amyloid-like fibrils with different lengths, to assess their suitability for nanotechnological applications such as bio-nanowires. This study has shown that structural resilience of the amyloid-like fibrils against unfolding by the electric fields is mainly dependent on their permanent dipole moment. Finally, we have also investigated the binding affinity of a potential chemotherapeutic drug to variants of cytochrome c, which is a known activator of the drug during its metabolism in the cell. This study has demonstrated that the presence or absence of hydration in the active site of the protein-drug complex may be important in determining the bioactivity of the drug. These diverse applications of atomistic molecular dynamics demonstrate its usefulness in both biotechnology and biomedicine.